Automatic treatment of pain

ABSTRACT

Disclosed are methods and medical device systems for automated delivery of therapies for pain and determination of need for and safety of treatment. In one embodiment, such a medical device system may comprise a sensor configured to sense at least one body signal from a patient; and a medical device configured to receive a first sensed body signal from the sensor; determine a patient pain index based at least in part on said first sensed body signal; determine whether said patient pain index is above at least a first pain index threshold; determine a safety index based at least in part on a second sensed body signal; select a pain treatment regimen based on at least one of said safety index and or a determination that said pain index is above said first pain index threshold; and deliver said pain treatment regimen.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.13/836,974, filed on Mar. 15, 2013, (published as US 2014-0276549), thecontents of which are incorporated herein by reference thereto in itsentirety.

FIELD OF THE DISCLOSURE

This disclosure relates generally to medical device systems and, moreparticularly, to medical device systems and methods capable of automateddelivery of treatments for pain.

DESCRIPTION OF THE RELATED ART

There have been many advances in the treatment of pain. In order tofacilitate faster delivery of pain medication to a patient, healthcareproviders have recently added a new dimension in delivering painmedication—machine delivery of medication. In addition to the manualdelivery of pain medication under a patient's control, medicationsystems can now be connected to an intravenous (i.v.) delivery systemthat can deliver medication without manual intervention by a healthcareprofessional. For example, healthcare providers may employ a painmedication delivery device that is capable of delivering a predetermineddosage of pain medication in response to a patient's request. Somedevices can operate under the control of a handheld unit, wherein when apatient depresses a button on a handheld unit, the pain medicationdevice pumps a predetermined dosage of medication to the patient,intravenously.

Although state-of-the-art pain medication devices are capable of rapidlydelivering medication to a patient, the delivery of these medications isgenerally based upon a pre-determined schedule and dosage or on apatient's subjective pain scale. In some cases, the predetermine dosagemay not be adequate, or maybe too high, resulting in inadequate painrelief, over-medication, or other health issues. Further, giving apatient full control of activating the delivery of medication may leadto over-usage of pain medication, which may have acute adverse effectssuch as cardio-respiratory depression, confusion or falls to the ground;addiction and chronic abuse of pain medications is also a commonconsequence of unregulated or careless administration of painmedications. Patients may self-medicate with pain medication forpsychological or pleasurable effects, not to alleviate pain. It would bedesirable to alleviate a patient's pain using methods and systemsthat: 1. Do not require intervention by medical practitioners or by thepatient; 2. Deliver the dose necessary and sufficient to relieve thepain while reducing over-usage of pain medication; 3. The method andsystem of delivery is prophylactic, that is, it prevents or anticipatesthe emergence of painful sensations effectively breaking the pain cycleand its associated suffering/distress, thus decreasing the probabilityof development of chronic pain syndromes.

SUMMARY OF THE DISCLOSURE

In one embodiment, the present disclosure provides a medical devicesystem, comprising at least one sensor configured to sense at least onebody signal from a patient; and a medical device configured to receiveat least a first sensed body signal from said at least one sensor;determine a patient pain index, wherein said patient pain index is basedat least in part on said first sensed body signal; determine whethersaid patient pain index is above at least a first pain threshold;determine a safety index wherein said safety index is based at least inpart on a second sensed body signal; select a pain treatment regimenbased on at least one of said safety index or a determination that saidpain index is above said first pain threshold; and deliver said paintreatment regimen.

In one embodiment, the present disclosure provides a method forproviding pain medication, comprising receiving, at a device, a requestfor delivery of a pain medication to a patient; receiving, automaticallyby the device, at least one body data series of said patient in responseto said request for delivery of a pain medication; determining a patientpain index based upon said body data series; determining whether thepatient pain index is above a reference pain index; determining a safetyindex; and allowing, automatically, delivery of a pain medication basedon at least one of said safety index or a determination that saidpatient pain index is above said reference pain index.

In one embodiment, the present disclosure provides a method forproviding pain medication to a patient, comprising receivingautomatically, at least a first body data series of a patient;determining a first discomfort index of the patient based upon saidfirst body data series; determining whether the first discomfort indexexceeds a first discomfort index threshold; and providing a firsttherapy in response to determining that said first discomfort index doesnot exceed said first discomfort index threshold.

In one embodiment, the present disclosure provides a method, comprisingreceiving at a device, a request for delivery of a pain therapy to apatient; receiving, automatically by the device, at least one body dataseries in response to said request for delivery of a pain therapy;determining a patient pain index based upon said body data series;determining whether the patient pain index is above a patient pain indexthreshold; and automatically delivering a pain therapy to the patient inresponse to determining that said patient pain index is above saidpatient pain index threshold.

In one embodiment, the present disclosure provides a method forproviding pain medication, comprising receiving at least one of arequest for delivery of a pain medication from a patient, an indicationof an elapsed time period, or a request for administration of aresponsiveness test to a patient; administering a responsiveness test tothe patient in response to said receiving; and allowing delivery of apain medication based on a determination that the patient'sresponsiveness is above a responsiveness threshold.

In one embodiment, the present disclosure provides a non-transitorycomputer readable program storage unit encoded with instructions that,when executed by a computer, perform a method referred to above.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a stylized depiction of a medication dispensingdevice, in accordance with one embodiment of the present disclosure;

FIG. 2 illustrates a stylized depiction of an alternative configurationof the medication dispensing device, in accordance with anotherembodiment of the present disclosure;

FIG. 3 illustrates a stylized block diagram depiction of the medicationdispensing device of FIG. 1 and FIG. 2, in accordance with oneembodiment of the present disclosure;

FIG. 4 illustrates a stylized block diagram depiction of the patientpain module of FIG. 3, in accordance with one embodiment of the presentdisclosure;

FIG. 5 illustrates a more stylized detailed block diagram description ofthe body data collection module of FIG. 3, in accordance with anembodiment of the present disclosure;

FIG. 6 illustrates a flowchart depiction of the steps for performing anautomated delivery of medication, in accordance with one embodiment ofthe present disclosure;

FIG. 7A illustrates a flowchart depiction of the steps for reacting to amedication request from a patient, in accordance with one embodiment ofthe present disclosure;

FIG. 7B illustrates a flowchart depiction of the steps for reacting to amedication request from a patient, including a safety determination, inaccordance with one embodiment of the present disclosure;

FIG. 8 illustrates a flowchart depiction of the steps for testing apatient pain threshold and taking subsequent action, in accordance withone embodiment of the present disclosure;

FIG. 9 illustrates a flowchart depiction of the steps for reacting to amedication request from a patient, in accordance with one embodiment ofthe present disclosure;

FIG. 9 illustrates a flowchart depiction of the steps for reacting to amedication request from a patient, in accordance with one embodiment ofthe present disclosure;

FIG. 10 illustrates a flowchart depiction of the steps for testing apatient pain threshold in response to at least one of a change a bodysignal, a change in the patient's emotional and/or mental state, time ofday, environmental conditions, time elapsed since the last therapydelivery and/or the type of therapy delivered to a patient, inaccordance with one embodiment of the present disclosure;

FIG. 11 illustrates a flowchart depiction of the steps for delivering apain treatment plan in response to a test of a patient's responsivenessand/or awareness, in accordance with one embodiment of the presentdisclosure;

FIG. 12 illustrates a flowchart depiction of the steps for deliveringtreatments for pain to a patient, in accordance with one embodiment ofthe present disclosure;

FIG. 13A illustrates the non-stationarity of pain thresholds, inaccordance with one embodiment of the present disclosure;

FIG. 13B illustrates the non-stationarity of pain thresholds, inaccordance with one embodiment of the present disclosure; and

FIG. 14 further illustrates the non-stationarity of distress thresholds,in accordance with one embodiment of the present disclosure.

While the disclosure is susceptible to various modifications andalternative forms, specific embodiments thereof have been shown by wayof example in the drawings and are herein described in detail. It shouldbe understood, however, that the description herein of specificembodiments is not intended to limit the disclosure to the particularforms disclosed, but on the contrary, the intention is to cover allmodifications, equivalents, and alternatives falling within the spiritand scope of the disclosure as defined by the appended claims.

DETAILED DESCRIPTION OF THE SPECIFIC EMBODIMENTS

Embodiments of the present disclosure provide for a medical device fordispensing therapeutic treatment, such as pain medication. The medicaldevice may be a standalone device that may be operatively coupled to adelivery mechanism (e.g., an i.v. infusion pump), which may be used todeliver treatment to the patient. In one embodiment, the medical devicemay include a portable device carried by the patient. In anotherembodiment, it may include an implantable device. The medical devices ofembodiments of the present disclosure may include various capabilitiesfor detecting one or more body signals (physiological or pathological)of the patient, analyzing these signals, using the results of analysisto assess the patient vital signs, neurological state, and the pain orsuffering/distress level, and automatically deliver therapy or, if thesystem is in a manual operation mode, grant the request if, based on theanalysis of the signals, therapy delivery is deemed both safe andnecessary. In one embodiment, the medical device may be capable offorecasting pain or distress levels and prophylactically andautomatically deliver medication, to prevent (conscious) pain perceptionor the suffering, distress and anxiety associated with the anticipationof pain. In this manner, delivery of medication is safe and timely withminimal or no interaction from the patient and is highly efficacious.The methods and systems described herein may reduce prevent or reducepain while limiting over-usage of pain medication, thereby keeping thepatient comfortable and reducing adverse effects of, or the potentialfor abusing pain medications.

Illustrative embodiments of the disclosure are described herein. In theinterest of clarity, not all features of an actual implementation aredescribed in this specification. In the development of any such actualembodiment, numerous implementation-specific decisions must be made toachieve the design-specific goals, which will vary from oneimplementation to another. It will be appreciated that such adevelopment effort, while possibly complex and time-consuming, wouldnevertheless be a routine undertaking for persons of ordinary skill inthe art having the benefit of this disclosure.

This document does not intend to distinguish between components thatdiffer in name but not function. In the following discussion and in theclaims, the terms “including” and “includes” are used in an open-endedfashion, and thus should be interpreted to mean “including, but notlimited to.” Also, the term “couple” or “couples” is intended to meaneither a direct or an indirect electrical connection. “Direct contact,”“direct attachment,” or providing a “direct coupling” indicates that asurface of a first element contacts the surface of a second element withno substantial attenuating medium there between. The presence of smallquantities of substances, such as bodily fluids, that do notsubstantially attenuate electrical connections does not vitiate directcontact. The word “or” is used in the inclusive sense (i.e., “and/or”)unless a specific use to the contrary is explicitly stated.

One of the benefits of utilizing such an automated system includes thefact that prior to full onset of pain, delivery of analgesic, anestheticor anxiolytic medications may take place, preventing onset of pain or,at a minimum, providing immediate relief. In order to achieve this,certain physiological signals or indices derived from such signals maybe recorded and analyzed in order to anticipate onset of pain orquantify it if already present. If delivery of pain medication iscontingent upon perception of pain by the patient, a “pain cycle” may beestablished. “Pain cycles” facilitate in certain patients chronic painsyndromes, a serious complication due to its detrimental effects on apatient's health, productivity and quality of life. Automated systemsprovided by embodiments herein may reduce or even substantially preventthe emergence of “pain cycles.”

Moreover, in other embodiments of the present disclosure, a request bythe patient for pain medication may prompt a physiological evaluation ofthe patient to be made in order to assess, using objective means, painlevel and also determine the safety of drug or other forms of treatment.Utilization of the automated system provided herein, decreases thepossibility of abusing pain medication and the acute and chronic adverseeffects of this behavior.

Before we turn to description of the various figures, several terms usedthroughout the disclosure will be described. Generally, a “pain level”as used herein refers to an amount of pain, as determined by subjectivereporting by a patient. The pain level indicates the consciousperception of intensity and quality of pain reported by the patient inverbal and/or non-verbal language and is associated with an emotionalstate and behavior that may or may not be strongly (positively ornegatively correlated) with the frequency, amplitude and pattern ofactivity of neuronal processes and systems responsive to noxiousstimuli.

A “pain index” refers to a value determined from a body signalindicative of and/or correlated with a pain level. Exemplary bodysignals may include blood pressure, heart rate variability, respirationrate, etc. Numerous other body signals are given infra. These signalsare usually outside the patient's realm of consciousness (i.e.,generally, the patient lacks awareness about them and as such thesignals are not verbally reportable).

Pain range refers to gradations of pain a patient may feel. A “painperception threshold” herein refers to a value or intensity of a noxiousstimulus at which a patient perceives pain of a particular magnitude orseverity and quality. Such a threshold, that is either directly orindirectly measurable/quantifiable, is a separatrix between either a) apain state and a pain-free state; or b) two or more pain gradations orlevels. Put another way, this disclosure acknowledges a multiplicity ofpain thresholds, rather than a single one.

“Empirical pain thresholds” may refer to an intensity and/or quality ofa stimulus applied during a test at which patient perceives pain thatmay be subjectively or objectively (e.g., using body signals) gradable.“Distress threshold” and “suffering threshold” are usually associatedwith higher pain levels or pain indices at which the patient is indistress and/or suffering, as discussed infra.

A “therapy threshold” herein refers to a pain level or a value of a painindex at which a therapy for pain is delivered. A pain index thresholdrelates to an objective measure derived from body data (e.g., heartrate, kinetic activity, etc.) at which pain therapy may be initiated. Apain index threshold may correspond to a patient's subjective “painthreshold,” or it may be different because, being subjective, painthresholds may fluctuate while pain index thresholds may only change bymanual programming or an adaptive response to factors, such as emotionalstate, fatigue, or the like, to maintain a desirable correlation withthe subjective pain threshold. A “discomfort index” herein refers to avalue determined from a body signal indicative of and/or correlated witha patient's physical discomfort level.

Turning now to FIG. 1, a stylized depiction of a medical device 100capable of delivering therapy, in accordance with one embodiment of thepresent disclosure, is illustrated. In one embodiment the medical device100 is external to the patient and capable of delivering medicationusing a variety of methods, such as an i.v., mucosal (e.g., nasal,rectal), serosal (e.g., peritoneum) or dermal interface. Alternatively,the medical device may be fully implanted into the patient's body todeliver a therapy (e.g., electrical stimulation, drugs) directly to atarget.

A medical device system may comprise one or more sensors 140 that areconnected to the medical device 100 via a communication means 130. Thecommunication means 130 may comprise various types of communicationconduits, such as medical leads, wires, wireless connection, etc. Themedical device 100 may also be coupled to one or more delivery points110, such points 110 each comprising a mechanism for delivering therapyto a location in or on the patient's body. In some embodiments, thedelivery point 110 may include a needle for delivering medication, acatheter, nasal prongs, etc. The delivery point 110 may be coupled tothe medical device 100 via a conduit 120 for delivering medication. Theconduit may be made from flexible bio-compatible material to conform tothe patient's body.

In one embodiment, the medical device system is capable of sensing oneor more physiological signals via the sensors 140. The sensors 140 mayrepresent a single sensor or a plurality of sensors capable of detectingvarious physiological signals. For example, the sensors 140 may includeone or more of autonomic signal (e.g., respiratory, cardiac, dermalactivity) sensors, neurological (e.g., EMG, reaction time, ocularactivity, oculo-vestibular activity) signal sensors, endocrine signal(e.g., cortisol) sensors, metabolic (pH) sensors, tissue stress markersignal (e.g., lactic acid) sensors, temperature sensors, sound/acousticsensors, etc. More detail regarding such signals and appropriate sensorsmay be found in U.S. patent application Ser. No. 12/896,525, herebyincorporated herein by reference.

Based upon analyses of the detected physiological or pathologicalsignal(s), the medical device 100 may make a determination whetherdelivery of medication is safe and appropriate. This determination maybe based upon a look up table, real-time or near real-time calculations,or may be based upon sending the physiological signal(s) to a deviceexternal to the medical device 100 and receiving feedback from theexternal device. For example, the medical device 100 may determine oneor more of a patient pain index, based at least in part on the firstsensed body signal, such as any of those referred to above; a safetyindex wherein the safety index is based at least in part on a secondsensed body signal, such as any of those referred to above, and whichmay be the same as the first sensed body signal; and whether the patientpain index is approaching, at or above certain first, second, third, orfourth, etc., pain, distress or suffering threshold(s) for the patient.

A patient pain index is used herein to refer to any objective bodysignal measurement correlated with pain. Exemplary objective body signalmeasurements include, but are not limited to, changes in heart rate,changes in heart rate variability, changes in respiratory rate,respiratory pattern, tidal volume, changes in dermal activity, changesin activity of facial muscles and muscle groups used in frowning,wincing, cringing, or other facial expressions suggestive of pain (e.g.,the corrugator supercilii) or distress/suffering, which may be measuredby electromyography (EMG) or imaging (e.g., video-thermography), voiceanalysis, the occurrence of non-formed vocalization or utterancesassociated with or suggestive of pain or of distress/suffering, changesin electrical, chemical, thermal brain activities or their outputfunctions (e.g., attention, memory, etc.), or the results ofresponsiveness and/or awareness tests. These changes in body signalvalues may be determined in reference to pain-free-state signal valuesin the absence of any therapeutic intervention as well in reference tothe cause of pain, site/location of pain and extent of body involvement,type of pain (e.g., burning, boring, electric-shock like), relation ofpain to body/joint position or level of activity, time of day, anxietylevel, age, gender, the psychological reaction of the patient to painand the patient's coping skills, personality type/psychological profile,or to other factors known to alter pain threshold/perception. Painindices may be also estimated in reference to other pain levels ordifferent pain types, yielding relative pain indices.

The various thresholds regarding the pain index may be based onquantitative or qualitative factors, e.g., they may reflect particularchanges in heart rate, heart rate variability, etc., and/or they mayreflect patient perception or conscious awareness, as well as the levelof distress or suffering the patient experiences. For example, in aninitial workup, the amount of pain which the patient perceives (is awareof if he or she so chooses, e.g., is mild enough to be ignored if he orshe so chooses) or is conscious of (is aware of regardless of his or herchoice, e.g., is intense enough that he or she cannot ignore it) may bedetermined and correlated with particular increases in heart rate, heartrate variability, etc.

Because the intensity, duration, or type/quality of stimuli required tocause pain or the susceptibility to feeling pain is not constant, thepain and/or distress/suffering thresholds vary as a function of one ormore of: a) time of day; b) level of consciousness (wakefulness v.sleep); c) level of cognitive activity (inattentive v. attentive); d)psychological status/personality; e) body site where pain occurs or towhere noxious stimulus/stimuli is/are applied when estimating painand/or distress/suffering thresholds; f) number of body sites and/orextent of body where pain occurs or to where noxious stimulus/stimuliare deliver to estimate pain and/or distress/suffering thresholds; g)type of treatment/drug and time of last treatment; h) efficacy oftreatment determined using subjective (pain scales) or objective (bodysignals); i) environmental conditions (e.g., room temperature); j)prevailing psychological conditions (e.g., tense situation); or k)changes in body signals indicative of pain as a function of the factorslisted in this paragraph.

Regarding perception or awareness of pain and the reaction (e.g.,suffering) to it, these phenomena occur when pain impulses reach thecortex (SS1, limbic system, and others). Blockage of pain impulses tothe cortex may prevent the perception and/or consciousness of pain. Theperception of pain may be associated with an emotional response ofdistress, discomfort, or suffering. If the emotional response istreated, the patient may experience relief even while perceiving pain.In several embodiments, this disclosure may address the emotionalcorrelates of pain and/or the blockage of perception of pain.

In one embodiment, the pain threshold is divided into or classified assubjective and objective. Subjective threshold is that at which thepatient is first aware of an uncomfortable or painful sensation, or ofan increase in said painful sensation, when noxious stimuli are beingdelivered at higher intensities (while taking precautions to avoidaccommodation/habituation) to a body part or location. Objective painthreshold is that at which changes in indices derived from body signals(e.g., cardio-respiratory, kinetic, dermal activity) compared to areference value, first occur or of a further increase in said indices orbody signal when noxious stimuli are being delivered at higherintensities (while taking precautions to avoid accommodation/habituationor injury) to a body part or location.

The subjective (e.g., what the patient reports) and objective (e.g., themagnitude of change and/or the rate of change in an index or bodysignal) thresholds are estimated by presenting noxious stimuli to thepatient at one or more body sites at different times and/or dates whilerecording the level of consciousness, psychological state of thepatient, and immediate (e.g., where the patient is at the time oftesting) environmental conditions among others. The difference innoxious stimuli intensity, if any, between the subjective and objectivethresholds is recorded and may be used to: 1) estimate the degree ofdiscrepancy between objective and subjective perception; or 2) use thisdifference for prophylaxis of pain. For example, if changes in bodysignals (or indices derived therefrom) occur under certain conditions atintensity levels below those associated with pain perception, therapymay be delivered as soon as changes in the body signal or index occur,preventing the perception of pain.

In another embodiment, pain perception by the patient and/or changes inindices or body signals are compared to the latency, magnitude(amplitude and duration), morphology, polarity, and topography of nerveroot, spinal cord, or brain responses elicited by the noxious stimuli.Analyses of these signals, a multi-variety approach to pain management,may provide valuable information about subjective and objectivecomponents of pain. Changes in the magnitude of the differences betweenthe subjective and objective threshold, or changes in any of thethresholds, may be used to assess pain status, issue a prognosis, ordetermine if there is progression or improvement. For example, if theintensity of noxious stimuli required to elicit pain perception and/orchanges in body signals decreases as a function of time, pain isworsening and measures may be instituted to decrease the probability ofevolving towards severe/chronic pain syndrome. The methodology todetermine a threshold entails the delivery of stimuli at the lowestpossible intensity (so-called sub-threshold intensities) and graduallyincrease said intensity, until pain is perceived or changes in bodysignals are recorded. Noxious stimuli may be electrical, mechanical(e.g., pressure), thermal or chemical. While only intensity has beenmentioned, other properties or characteristics such as quality,frequency, duration, etc., may be varied to determine thresholds.

Other thresholds may be used (and determined) in this disclosure for thepurpose of managing pain to minimize or abolish not only this sensationbut its associated distress or the feeling of suffering,intolerability/un-endurability (e.g., when pain becomes unbearable,agonizing). Distress/discomfort and suffering/intolerable/agonizing areregarded as being distinct from each other in this disclosure and eachstate may be also classified as subjective and objective. Subjectivedistress threshold is the intensity or stimulus property/characteristicat which the feeling of distress is first felt or perceived. Anobjective distress threshold is the intensity or stimulusproperty/characteristic at which body signals (or indices derived fromthem) susceptible to influence by distress further change or reach aparticular value indicative of distress.

Subjective suffering threshold is the intensity or stimulusproperty/characteristic at which the feeling of suffering/intolerabilityis first felt and an objective suffering threshold is the intensity orstimulus property/characteristic at which body signals/indicessusceptible to influence by suffering further change or reach aparticular value indicative of suffering. The intensity or properties ofthe noxious stimuli required to elicit the perception of non-distressingpain, of distressing but bearable pain, or of suffering/unbearable painmay be the same or different for a given patient and may vary as afunction of time of day and psychological state, among other factors.These findings sheds light and insight into the psychological make-up,pain coping mechanisms and resilience of the patient to pain and mayhelp shape the pain management strategy and the issuance of prognosis(e.g., will the patient develop a chronic pain syndrome?). It is commonknowledge or experience that the sensation of pain (depending on itsintensity, type, location, time of day, level and type of activity theperson with pain is engaged in, the person's mood, environmentalconditions, etc.) may be ignored and the person may continue to functionnormally, or the pain may be bearable but cause distress and affect theperson's functional capacity to some extent, or the pain may becomecrippling/insufferable and the person is unable to engage in anyactivity, the pain becoming the sole focus of that person's attention orlife. It is also known that the higher the intensity or the more noxiousthe stimulus, the more distress or suffering is experienced by thepatient. It is therefore useful for treatment and prognostic purposes todetermine if there are differences in the intensity or properties ofstimuli that elicit the sensation of: a) pain only; b) pain anddistress; c) pain and suffering. If a stimulus intensity that initiallycaused only pain now causes distress or suffering, this points to aworsening of the condition. While as stated above, theintensity/properties of the pain play a role in determining whether ornot distress or suffering ensue, other factors innate to the person andto the environment may also shape the response. Distress and sufferingthresholds may be determined using the methodology for determination ofsubjective and objective thresholds.

A subject's ability to perform certain physical tasks (e.g., perform acertain range of joint motion, lift a certain weight, walk a certaindistance at a certain speed) or cognitive tasks (e.g., complex reactiontime tests, attention span tests) may be also used to grade theintensity of pain and its impact of the subject's functional abilities.

A safety index is used herein to refer to a quantitative estimate of thesafety of a pain treatment. For example, the safety index may depend onone or more of the pain treatment regimen (e.g., type, specific drug ifthe type is medications, dosages of drugs, rate of administration,etc.), the patient's age, weight, body mass index (BMI), sex, otherhealth conditions, wake/sleep status, etc. A safety index may becalculated or determined using at least one of the body signals that aresusceptible to change by drugs or therapies for pain; vital signals(e.g., heart rate, blood pressure), cognitive functions (e.g.,performance on complex reaction time tests, responsiveness tests, orawareness tests; or indicators of alertness or drowsiness),vestibulo-cerebellar functions, are among those most affected byanalgesics. Such signals and indicators may be considered by theirabsolute value (e.g., an indicator of a particular level ofconsciousness or of greater of drowsiness may be taken into account whenadministering a CNS depressant drug) or their relative value (e.g., adecrease in heart rate of n beats per minute below baseline may be takeninto account when administering a narcotic). For example, an increase inmean latency in response time to reaction time tests may be used toquantify a change in safety index. In general, a safety index may becomputed, for example, as the algebraic sum of changes in value in oneor more values determined from body signals, compared to reference(off-drugs) values.

Returning to FIG. 1, the medical device 100 may be capable of receivinginputs from the patient for a request for medication. The input may bereceived via the sensors 140, or other type of input means, such aswireless communication means, tap sensors, magnetic sensors, etc. Basedupon a request from the patient, the medical device 100 may perform anevaluation of one or more physiological or pathological signals of thepatient's body to determine whether it would be safe and appropriate todeliver medication to the patient. In this manner, abuse of painmedications may be curtailed and the patient's safety protected. If adetermination is made from the analysis of the physiological orpathological signals that there are no detectable pain correlates, themedical device 100 may not deliver medication to the patient. Further,the medical device 100 may automatically log to memory and/or reportthis event to a predetermined location, such as a nurse's station ormonitoring center. A medical professional may retrieve this informationto evaluate the patient's behavior tendencies, treatment efficacy, etc.

For the sake of clarity regarding the use of “safety” and “drugtolerance” herein, because the present disclosure is focused on painmanagement, such as by drugs that relieve pain (e.g. narcotics), theterm “tolerance” is used herein to describe a therapy's loss ofanalgesic effect with repeated administration. Unpleasant or deleteriousside effects that may be caused by the therapy are considered here underthe rubric “safety.” “Safety” also means no drop in vital signs to alevel that may cause physiological dysfunction to the patient and/orlethargy, confusion, incoordination, falls or injury.

Discussions herein of tests of safety take into account the presentcondition of the patient and, based on that condition, pain therapy maybe withheld or modified. As a hypothetical, non-limiting example,consider an elderly patient with a baseline resting blood pressure of140/90; pulse of 80; respiratory rate of 12, cognitively intact, nomotor or visual deficits, and in pain with no prior treatment for it.Beginning automatic delivery of a narcotic while monitoring the vitalsigns, it may happen that after 3 mg of fentanyl, the patient's bloodpressure drops to 110/60; infusion may then be stopped since it iscausing “hypotension” for that individual. For another example, considerthe same patient awake and ambulatory at home, when fentanyl infusionbegins. After 5 mg, the patient becomes drowsy (as determined by areaction time test) and unsteady (as determined by bodysway/oscillations recorded with an accelerometer when he stands up,oscillations that had not been present before administration of saiddrug). In this case, infusion may be stopped, a warning may be issued,and data may be logged for later use by a physician to determine whetherdifferent drugs should be used or whether the dose or rate of fentanyldelivery should be reduced to lower the likelihood of adverse effects.

The medical device 100 may store information relating to a particularpatient, so that analysis of the patient's physiological information maybe customized to that patient. This analysis may be dynamically adjustedso that more accurate evaluation and analysis of the patient'sphysiological information may be performed. This dynamic adjustment maybe performed contingently (e.g., triggered by a request for medicationor when there is a change in physiological signals) and/or periodicallyby a healthcare professional or automatically.

In one embodiment, if the medical device 100 determines that painmedication is warranted (e.g., based on one or more body indices), andthat its delivery would be safe to the patient, with or without beingprompted by a request by the patient, the medical device 100 may begin amedication delivery process. For example, the medical device 100 mayactivate a mechanical process to release stored medication from areservoir. The medication may be delivered via the conduit 120 to thedelivery point 110 to medicate the patient. The decision to deliver themedication, type of medication, dose, rate of delivery as well as thetime of occurrence of the delivery, may be logged and/or reported to apredetermined target, e.g., the patient's physician. The automation andcontrol afforded by the medical device 100 allows this system to besafely used in locations that are remote from the healthcare facilities,e.g., usage in a home-health context.

Although FIG. 1 refers to the delivery of pain medication, the medicaldevice 100 may be configured to deliver any pain treatment, notnecessarily a pain medication. For example, the medical device may beconfigured to select a pain treatment regimen comprising at least one ofa medication, a dose of the medication, a delivery route of themedication (e.g., intravenous or intrathecal), a cocktail ofmedications, a dose of the cocktail, a delivery route of the cocktail(e.g., intravenous, intrathecal, or intracerebral), an electricalstimulation, at least one parameter of the electrical stimulation, atarget tissue of the electrical stimulation, a cognitive therapy (e.g.,biofeedback/operant conditioning, or psychotherapy, among others), atleast one parameter of the cognitive therapy, a biofeedback, at leastone parameter of the biofeedback, a thermal manipulation, at least oneparameter of the thermal manipulation, or a target tissue of the thermalmanipulation; and deliver the pain treatment.

Also, the medical device may be further configured to make otherdeterminations and/or act upon any determinations it may make. Forexample, the medical device may be further configured to determine abody tolerance index relating to a first medication or other form oftreatment for the patient based at least in part on a history of thepatient or a patient response to an exogenous painful stimulus. Themedical device may be configured to select the pain treatment regimenbased at least in part on the determination of the body tolerance index.Body tolerance may be assessed by measuring changes in the subjective orobjective thresholds (pain, distress, suffering) to noxious stimuliusing the approach described previously under different conditions, asbody tolerance to drugs or other forms of treatment may vary as afunction of one or more of a) time of day; b) level of consciousness(wakefulness v. sleep); c) level of cognitive activity (inattentive v.attentive); d) psychological status; e) body site to where noxiousstimulus/stimuli is/are applied for the purpose of determining a painthreshold and assessing the development and degree of tolerance to atreatment; f) number of body sites stimulated; g) type or quality ofnoxious stimulus; h) type of treatment/drug, dose and time of lasttreatment; i) changes in body signals indicative of pain (accommodationmay occur in this signal); or j) psychological or genetic makeup.

The medical device system may further comprise other components. In oneembodiment, the medical device system may comprise an accelerometerconfigured to sense movement of the patient. Information provided by theaccelerometer may be useful in adaptively adjusting the pain, distress,or suffering thresholds based on the patient's kinetic activity level(e.g., body movements), thus increasing specificity of pain detectionusing body signals, since physical activity and pain may alter bodysignal values. Use of an accelerometer, EMG, mechanogram, actigraph,imaging tools, or means of measuring force or work may be used toidentify the degree to which changes in body signal values are due topain or physical activity. Also, information derived from kineticsignals may be useful in validating or illuminating other objective dataabout pain and efficacy of a therapy. For example, some pain isassociated with hypermotoric (increased) activity, such as pacing orfidgeting, whereas other pain is associated with hypomotoric (decreased)activity (movement worsens pain) compared to reference values. The onsetof hypermotoric or hypomotoric activity may indicate the onset orworsening of pain, and a decrease in hypermotoric activity and/or anincrease in hypomotoric activity after treatment may be indicative ofefficacy.

Turning now to FIG. 2, an alternative implementation of the medicaldevice 100, in accordance with one alternative embodiment of the presentdisclosure, is illustrated. In an alternative embodiment, the medicaldevice 100 may be a separate standalone device that is coupled to thepatient via a conduit 120, which connects the medical device 100, whichin the depicted embodiment is shown mounted or otherwise connected to arolling stand 250 to which bags or other containers of pain medicationmay be mounted. Conduit 120 may be coupled to the patient at thedelivery point 110. In the embodiment illustrated in FIG. 2, the medicaldevice 100 may receive physiological signals from the patient from asensor 230, which may be capable of sensing one or more signalsindicative of the patient's body data such as heart rate, bloodpressure, respirations, responsiveness level/reaction time, kineticactivity, etc. The sensor 230 may be a wireless device that may be incommunication directly with the medical device 100.

Alternatively, the sensor 230 may be in communication with anintermediate device 240 that is capable of receiving signals from thesensor 230 and transmitting signals to the medical device 100. Theintermediate device 240 may be a signal repeater device, a signalamplifying device, a handheld device, a cell phone device, a personaldigital assistance (PDA), a computer device, or a wrist device, such asa smart wristwatch. Alternatively, the intermediate device 240 may be astandalone device, such as a laptop computer, a receiver/transmitterstation, etc. As described above, the medical device 100 may receivephysiological signals from the sensor 230 and/or the intermediate device240, and may perform an evaluation as to whether or not to delivermedication to the patient. For example, in a patient care facility, suchas a hospital, the medical device may be connected via a catheter to thepatient wherein the patient is free to move the medical device using acart and be free to move about the medical facility. All the while, thesensor may be in communication with the medical device 100 (oralternatively the intermediate device 240) such that the medical device100 is capable of automatically delivering pain medication based on theanalyses of body signals and, in some embodiments, one or more safetyindices. A warning may be issued to a caregiver if delivery is deemedunsafe or unnecessary. In an ambulatory patient (one that is not understrict bed rest orders), warnings may be issued to caregivers if vitalsigns, confusion or unsteadiness are detected. This action allowscaregivers to take steps to prevent falls and injuries.

In an alternative embodiment, the patient may provide an input to themedical device 100 via, for example, the intermediate device 240, torequest medication. The medical device 100 may then perform anevaluation of the physiological signals received from the sensor 230 todetermine whether it would be appropriate to provide medication. Thedosage may also be adjusted based upon the evaluation of thephysiological signal before medication is delivered to the patient.Alternatively, in response to the patient's request for medication, thephysiological device may be transmitted (e.g., the intermediate device240) to a healthcare professional. The healthcare professional may thenrespond back to the medical device 100 (either directly or via anotherdevice, e.g., the intermediate device 240) by prompting delivery ofmedication at a particular dosage, or denying the delivery of the (orany) dosage.

Turning now to FIG. 3, a block diagram depiction of the medical device100, in accordance with one embodiment of the present disclosure, isillustrated. In one embodiment, the medical device 100 comprises amedication controller 310, a communication unit 320, a medicationreservoir 330, a medication dispenser 340, a body data collection module350, memory 360, the power supply 370, and a patient pain module 380.One or more of the blocks described in FIG. 3 may be a standalonehardware unit, a software unit, and/or a firmware unit.

The medication controller 310 may comprise one or more processors,controllers, programmable gate arrays, and/or ASIC modules. Themedication controller 310 is capable of controlling various operationsof the medical device 100. The medication controller 310 is capable ofreceiving signals indicative of pain level/intensity from the patientpain module 380. The patient pain module 380 is capable of processingone or more physiological or pathological signals from the patient'sbody, and/or an external signal in order to determine at least one of apain index or a pain level. The patient pain module 380 may also becapable of determining whether the patient's subjective threshold orpain scale is supported by or in agreement with an objective thresholdbased on body signal data. Based upon an indication of a pain levelexperienced by the patient, the medication controller 310 is capable ofmaking a determination whether it would be appropriate (i.e., indicatedand safe) to provide medication to the patient at a particular timeperiod. Autonomic and neurologic indices (e.g., kinetic, reaction time,EEG, etc.), among others, may be used to “validate” the perception ofpain by a patient. Autonomic indices include but are not limited to:electrodermal/sudomotor activity, pupillary size, pupillary hippus, orR-R variability, among others.

The medication controller 310 is also capable of controlling theoperation of the medication dispenser 340 and the delivery of medicationfrom the reservoir 330. The reservoir 330 is capable of storing one ormore medicinal compounds. In one embodiment, one of more medicinalcompounds may be available in the reservoir 330 and mixed beforedelivery of medication. In one embodiment, the reservoir 330 is capableof storing medication in a variety of environmental conditions, e.g.,refrigeration, pressurized conditions, etc. The reservoir 330 may havemultiple compartments, each containing a type medication that isdifferent from that in other compartments. The controller 310 mayautomatically dispense simultaneously more than one drug (a drug“cocktail”) in the appropriate dose, depending on the patient's clinicalstatus, pain level and type. In another embodiment, the medical device100 may be also endowed with electrical, thermal, orcognitive/biofeedback treatment capabilities that may be used alone orin any possible combination.

The medication controller 310 may incorporate look up tables or otherinformation in the memory 360 with regard to a particular patient'sprofile and the schedule of medication delivery and dose for aparticular patient based upon certain variables. These variables includepain, distress, or suffering thresholds, therapy tolerance thresholds,and safety considerations (occurrence of adverse effects, their type andseverity, etc.). The medication controller 310 may also performcalculations about dose and delivery schedules, based on factors such asage, gender, body mass index, fitness level, neurologic index values(e.g., kinetic, reaction time, presence and amplitude of body sway whenin the upright position, presence and amplitude of nystagmus, etc.),autonomic index values (e.g., blood pressure, heart rate, respiratoryrate, oxygen saturation, etc.), time from last dose and type dose ofdrug administered.

The medical device 100 may also comprise a communication unit 320capable of facilitating communications between the medical device 100and various devices. In particular, the communication unit 320 iscapable of providing transmission and reception of electronic signals toand from sensors 130 external to (or implanted within) the body and/orfrom other external computing devices, such as a handheld computer, alaptop computer, a workstation, a desktop computer, or PDA in wired orwireless communication with the medical device 100. The communicationunit 320 may include hardware, software, firmware, or any combinationthereof. The communication unit 320 may comprise various components thatare capable of providing for communication to and from the medicaldevice 100. For example, interaction between medical device 100 and ormore sensors 130, 230, or an external device 390 may be facilitated bythe communication unit 320. The communication unit 320 is also capableof providing for wireless and wired communications between variousdevices and the medical device 100. These communications sessions mayinvolve network communications or wireless communications, such asWI-FI, Bluetooth, RF, or other type of wireless communication.

In one embodiment, a medication dispenser 340 is capable of deliveringmedication, at a pre-specified dose and rate, from the medical device100 to the patient. In one embodiment the medication dispenser 340 maycomprise one or more pumping components that are capable of deliveringmedication from the reservoir 330 to a patient's body. The medicationdispenser 340 may comprise hydraulic components, micro-machinecomponents, solid state devices, electromechanical components and/or thelike. The operation of the medication dispenser 340 may be controlled bythe medication controller 310.

The patient pain module 380 may also comprise a body data collectionmodule 350. The body data collection module 350 is capable of collectingvarious types of body of physiological or pathological data. A moredetailed description of the body data collection module 350 is providedin FIG. 5 and accompanying description below.

The patient pain module 380 may comprise one or more processors,controllers, etc., capable of determining whether a particular patient'spain level is above, at, or below a predetermined pain threshold fordrug delivery. Information regarding a particular patient may be storedin the memory 360, which may be utilized by the patient's pain module380 to perform such analysis. Based upon various body data provided bythe sensors 130, the patient pain module 380 may make one or morecalculations to determine whether one or more body signals indicate thatthe patient is experiencing pain above a predetermined threshold.Further, if the patient pain module 380 were to determine that a painindex or pain level is above a threshold level, this information may beprovided to the medication controller 310, which may activate themedication dispenser 340. Power for operation of the medical device 100may be provided by a power supply 370, which may comprise one or morebatteries and/or external power source. In some embodiments, powersupply 370 may be rechargeable by using an external power source, awireless inductive power source, capacitive power source, etc.

Various information, such as operation algorithms, instructions, etc.,may be provided to the medical device 100 via an external device 390.The external device 390 may comprise a computer system, a controller,medication delivery devices, etc. The external device 390 may be adevice that is capable of programming various modules and units of themedical device 100. The external device 390 may be controlled by ahealthcare provider, such as a physician, at a base station in, forexample, a nurse's station or a doctor's office. The external device 390may be a computer, such a handheld computer, a PDA, a smartphone, etc.,but may alternatively comprise any other device that is capable ofelectronic communications and programming. The external device 390 maydownload various parameters and/or program software into the medicaldevice 100 for programming the operation of the medical device 100. Theexternal device 390 may also receive and upload various statusconditions and other data from the medical device 100. Communicationsbetween the external device 390 and the communication unit 320 may occurvia a wireless or other type of communication.

Turning now to FIG. 4, a block diagram depiction of a patient painmodule 380, in accordance with one embodiment of the present disclosureis illustrated. The patient pain module 380 is capable of processing avariety of types of body data. The patient pain module 380 comprises apain index determination unit 410, a body data lookup unit 420, apatient/caregiver input unit 430, a pain level determination unit 440,and a pain index comparison unit 450. A pain index may be computed asthe difference or the ratio between observed and reference values of abody signal. For example, if the heart rate in patient in a recumbentposition during a pain-free period is 65 bpm (reference value) andsometime later with the patient in the same position it is 85 bpm, thevalue of the pain index is +20 (the difference) or 1.3 (the ratio). Ifthe difference between observed and reference value is used to set thetherapy threshold, under those specific conditions (e.g., recumbentposition) at 80 bpm, a therapy will be automatically delivered, if safe,when the recumbent heart rate reaches 80 bpm (if no duration constraintis applied). Duration constraints may be imposed for any threshold-basedautomated action or decision to avoid false detection of pain thresholdsassociated with short-lived non-specific perturbations in indices orbody signals of interest. Therapy delivery may be governed not only by apain index value (e.g., the heart rate reaching 80 bpm in this example)but also by time; the caregiver may decide that therapy will bedelivered only if the heart rate remains at a minimum at 80 bpm for 15sec. This time constraint may be also applied to changes in painindices, where a change in value leads to an action only it remains at acertain value for a certain duration (>0 sec.)

The pain index determination unit 410 may determine one or more painindices based upon the body data received by the medical device 100. Forexample, various types of body data, such as autonomic data,neurological data, endocrine data, metabolic data, tissue stress markerdata, etc., may be processed and analyzed by the pain indexdetermination unit 410. The autonomic data may include heart beat data,blood pressure data, respiration data, blood gas data, etc. Theneurological data may include kinetic patient data, such as data from anaccelerometer or an inclinometer, etc. Other types of neurological datamay include data about the level of responsiveness or awareness of thepatient. Additional types of neurological data include facial mimeticdata. Further endocrine data, metabolic data, and various tissue stressmarker data may be analyzed by the pain index determination unit 410.The body data received by the body data collection module 350 (FIG. 3)may be analyzed and organized by the pain index determination unit 410.

In one embodiment, a pain index may be calibrated, validated, orcorroborated by delivering noxious stimuli to the patient. Thedetermination of a pain threshold, which may span a wide range (e.g.,FIGS. 13A-13B), may be prompted by a change in at least one body signalor it may be performed according to a pre-specified schedule, or at thepatient's or caregiver's discretion. To determine a pain perception,distress or suffering threshold, the patient may be fitted with a deviceor apparatus that generates uni- or multi-modal noxious stimuli and themode(s) will be selected based on the patient's description of painquality (e.g., burning, boring, electric-shock like). This device maygenerate one or more of mechanical (e.g., pressure, friction), thermal(e.g., cold, heat), visual (e.g., light colors and/or intensities),acoustic (e.g., loud high pitch sounds), chemical (e.g., capsaicin), orelectrical stimuli that are applied in a desired combination of modesand/or intensities to mimic the patient's perceived pain, to moreaccurately characterize the patient's pain threshold(s). The minimumnoxious stimulus intensity required to cause a painful sensationestablishes the pain, distress or suffering thresholds at the time thetest is administered. Because the duration of application of the painstimulus can itself affect the pain threshold established by the test,the stimulus intensity may be increased (rapidly or slowly) during thethreshold test(s).

Additionally, the conditions of the patient's immediate environment maybe modified during the pain threshold test to more closely resemblethose to which the patient is more often subjected, (or will be exposedto upon discharge from a medical facility) to better tailor a paintreatment plan specific to the patient. For example, if the patient'senvironment is acoustically noisy, determination of pain threshold maybe made under acoustically noisy conditions. To better treat a patient,the determination of pain threshold may be made while presenting stimuliwith negative emotional content (e.g., fear, anxiety, etc.) in the formof visual, auditory, olfactory, or tactile stimuli in any desiredcombination, since these negative stimuli tend to alter pain, distressor suffering thresholds. When establishment of distress and/or sufferingthresholds are impractical or impossible, changes in these thresholdsmay be inferred from changes in the pain perception threshold as well asthrough administration of psychological, emotional and other tests.

Consider the following hypothetical example. A patient reports anincrease in pain: a) from being free of pain to a “first”/lowest painlevel (e.g., perception of tolerable pain); b) from first to“second”/intermediate pain level (from tolerable to intolerablepain/distress); c) from second to “third”/highest level (e.g., fromdistress to suffering) (Notice that progression need not be continuous(e.g., 1^(st) to 2^(nd) and 2^(nd) to 3^(rd)), but may be discontinuous(1^(st) to 3^(rd)). In response to said increase in pain, noxiousstimuli are delivered to patient whom is asked to grade their intensity.The response is compared to reference values (obtained at earlier timesunder certain conditions (e.g., time of day, time from last dose, mood,etc.) and used to determine if the pain intensity has indeed increasedor if the sensory or the pain thresholds have decreased. For example, athermal stimulus (heat via laser) may be applied to the dorsum of thepatient's left hand and its threshold for perception is determined(“tell us when you feel heat”), while body signals may be simultaneouslymonitored and used in a quantitative comparison. If the patientperceives the heat at a lower intensity than before, the threshold isnow lower. It may not be ethical (or useful) to determine distress orsuffering thresholds, but this is not necessary, since changes insensory or in the lowest pain threshold are likely reflect changes inthe distress and suffering thresholds. Reflex responses such as rapidwithdrawal of an extremity form the pain source, or actions to shield itfrom said source, may be used instead of verbal responses.

Sensory threshold in this disclosure is the lowest stimulusintensity/energy eliciting a conscious sensation; furthermore, sensorythreshold is herein divided into painless and painful, a division thattakes into account the fact that under normal conditions, that may ormay not apply to patients with pain, the stimulus intensity or energy,and thus the threshold, required to elicit a non-painful sensation islower than that required to elicit a painful one.

Returning to the hypothetical example immediately above, patients may bealso presented with images, sounds, smells, or narratives with negativeemotional (or positive) emotional contents and their subjective andobjective responses (body signals) recorded and logged for comparisons,for determination of the stability (or lack thereof) of pain or otherthresholds and indirectly of pain levels. This allows estimation of the“emotional” threshold and may be used to anticipate and prevent theperception of pain or its escalation into distress or suffering. Thesame comparison may be made when pain is improving (e.g. 3^(rd) to2^(nd) level) and this information may be used to modify the therapy inadvance of the expected change.

“Emotional state” herein refers to either a subjective state reported bythe patient, that the patient can generally label as being eitherpositive or negative, to which greater “granularity” may be added usingnumerical, pictorial or other scales. When exogenous factors (e.g., timeof day, ambient temperature, noise level, etc.) are known, changes inbody signals and based on them, changes in pain indices may be betterinterpreted, for more accurate correlation with pain levels (e.g.,tolerable, distress, or suffering) or pain thresholds. By taking suchexogenous factors into consideration in some embodiments, body signalsand/or pain indices may be more effectively employed either to preventtransitions from one pain level to another (including the transitionfrom a pain free into any of the other pain states) or to instituterapid treatment if prevention of the transition is not feasible.Exemplary changes may be in the body signal's magnitude, rate of change,direction (e.g., increase/decrease) and/or duration compared to areference value.

As should be apparent, the patient's pain threshold and related conceptsare generally nonstationary.

The results of patient pain threshold testing may be used to selectthose indices that best reflect the presence and intensity/quality ofpain, to calibrate or adjust pain indices, to set pain index thresholds,and/or to make decisions about the type, dose, and schedule of deliveryof a pain treatment regimen.

Determination of pain threshold(s) may be performed to: 1. deliveranalgesic therapy prophylactically to the patient before the painthreshold decreases to a level likely to be associated with theperception of pain, or before the pain causes a certain level ofdistress, in response to a change in its value indicative of its closerproximity to an undesirable value (FIG. 14, prophylactic treatment) orsymptomatic (i.e., it relieves the patient's distress) (FIG. 14,symptomatic treatment.); 2. minimize both intensity and duration of theexperience of pain if prophylaxis is not possible.

It should be noted that herein, pain intensity and pain threshold aretreated as variables. Pain intensity is used herein to refer to thefrequency and amplitude of neural impulses traveling through thespino-thalamic and other tracts mediating the sensation of pain. Painthreshold is used herein to refer to the inherent level at which certainimpulses are perceived as pain by the patient, and may vary according tomany factors such as time of day, medications taken by the patient, age,sex, genetic factors, psychological factors, health and fitness levelsof the patient, etc. Certain thalamic strokes manifest with spontaneousand continuous pain on the side of the body contralateral to the stroke;this is an example of reduction in the pain threshold to the point thatnon-noxious stimuli (e.g., touching the patients skin) become painful.Allodynia is another example of reduction in pain threshold. Painintensity may vary but one or more pain thresholds (pain, distress,suffering, etc.) may remain constant, or pain intensity may remainconstant but one or more of the thresholds may vary (increase ordecrease).

This comprehensive approach disclosed herein, which takes into accountan ignored patho-psycho-physiologic feature of pain, may be used toprovide more intelligent and better management of pain, as it allowsanticipation of changes in pain perception and the patient's response,and for the prevention and/or prophylaxis of such changes, and thepatient's responses thereto. Changes in the threshold for distress orsuffering may also occur throughout the day as a function not only offactors associated with circadian rhythms but also of the psychologicaland physical environments/conditions. For example, intense heat andbeing in a crowded noisy and tense environment may precipitate a senseof distress or even suffering in someone who is in pain or may make painthe center of attention in someone who was previously “indifferent” toit.

Further, the patient pain module 380 may acquire data from the memoryfor categorizing and analyzing the body data. For example, body datalookup unit 420 may interface with the memory 360 (FIG. 3) to performvarious lookup functions, such as table lookup, etc. The pain indexdetermination unit 410, in conjunction with the body data lookup unit420, may analyze, process, or otherwise prepare a pain index value foruse by further units of the patient pain module 380.

Moreover, an input by the patient or a caregiver relating to a requestfor a therapy may be detected by the patient input unit 430. The patientinput unit 430 may determine the frequency of any requests from thepatient for therapy, a dose delivered in the most recently providedtreatment, time elapsed since the last treatment, etc., in performingthe pain analysis.

The pain level determination unit 440 is capable of determining a painlevel experienced by the patient based at least in part on input fromthe patient. In contrast to pain indices derived from body data of thepatient, the pain level has at least a partial subjective component. Forexample, the pain level may be determined from pain scales,questionnaires, or the like. Alternatively or in addition, the painlevel may encompass indicators of patient distress, i.e. psychological,social, and/or spiritual concerns that can extend from feelings ofvulnerability, sadness, and fear, to depression, generalized anxiety,panic, isolation, despair, or a spiritual crisis. Emotional correlatesof pain such as suffering, distress, etc., may be determined byrecording body signals indicative of levels of activity of thepatient's: a) kinetic activity (e.g., fidgetiness, restlessness); b)facial mimetic expression (e.g., frowning, crying, etc., any of whichmay be recorded using electromyography (EMG) of the effecting muscles oran imaging modality (visual, infrared, etc.) of the facial expression);and/or c) autonomic system (e.g. dermis, cardio-vascular, respiratoryactivity), so that a pain level may be estimated. The following scalesmay be used to aid in the assessment of levels of pain and distress:McGill Pain Questionnaire; Facial expressions; Happy/sad face graphicpain scale; Analog scale for patient self-assessment; Numeric RatingScale; Wong-Baker Faces; COMFORT Scale; CRIES Pain Scale; FLACC Scale;Checklist of Nonverbal Indicators; Pictorial representation of illnessand self-measure; Visual Analog Scale; Graded Chronic Pain Scale; theHospital Anxiety and Depression Scale and the Insomnia Severity Index;Likert scale; Functional Assessment of Chronic Illness Therapy-SpiritualWell-Being; Edmonton Symptom Assessment Scale; Structured InterviewAssessment of Symptoms and Concerns in Palliative Care Distress;Hamilton Depression Rating Scale; Will to Live and Desire for DeathVisual Analogue; Schedule of Attitudes toward Hastened Death; Desire forDeath Rating Scale. Other means to assess distress, depression and/orsuffering and their impact on the patient are (listed in no particularorder):

Mini-Suffering State Examination (MSSE). Total mood disturbance scoresof the Profile of Mood States, FACIT-Sp, Schedule of Attitudes towardHastened Death, Desire for Death Rating Scale, The FACIT Quality of Lifemeasure, the Missoula-VITAS Quality of Life Index, the McGill Quality ofLife tool, the QUALE, the EORTC questionnaires/(QLQ-C15-PAL), theFunctional Assessment of Cancer Therapy modules, the Quality of LifeScale, the Diagnostic Interview Schedule, the Composite InternationalDiagnostic Interview, the Schedule for Affective Disorders andSchizophrenia, the Endicott Substitution Criteria, the DiagnosticInterview Schedule, the Composite International Diagnostic Interview,the Structured Clinical Interview for DSM-IV, the Beck DepressionInventory-13 items, the General Health Questionnaire, the Hospitalanxiety and depression scale, the Centre for Epidemiologic studiesdepression scale, Hospital anxiety and depression scale, Beck DepressionInventory-II, the Palliative care outcome scale, theState-of-Suffering-V, or the so-called distress thermometer. A distresslevel threshold may be variable, being subject to influences similar tothose that affect the pain perception threshold as discussed herein.

Based upon various characteristics of the body data, the patient painindex value may then be compared to a pain level or to a pain thresholdby the pain index comparison unit 450, so that a degree of concordancebetween them may be determined (e.g., whether the pain index iscommensurate with the pain level). For the comparison, the pain indexvalue determined from body data may be compared to index valuesassociated with one or more of the patient's pain level threshold,distress threshold, or suffering threshold to determine whether atherapy should be provided to the patient. Because the various painlevels and thresholds are non-stationary, the pain index value may beweighted before comparing it to the level or to the threshold(s) (e.g.,the pain index can be given more weight the higher the concordancebetween it and the prevailing pain level experienced or reported by thepatient), and/or the changes in threshold(s) detected and the treatmentplan adjusted in light of said changes.

The therapy threshold for at which a therapy may be delivered to thepatient may be provided to the pain index comparison unit 450 by thememory 360. Upon a comparison of the pain index and the predeterminedthreshold, the pain index comparison unit 450 may provide data as towhether a predetermined pain threshold has been crossed. Based upon thepatient pain index reaching or exceeding the pain index threshold, themedical device 100 may deliver automated, predetermined therapy to thepatient. Further, the medical device 100 may also store and report thisaction, and receive and act upon any instructions based upon thereporting. In one embodiment, subjective pain scales in an electronicdevice capable of communicating with pain input unit 430 may be used(subject to validation using body signal analyses) to aid in themanagement of pain.

A number of factors may influence pain levels experienced by thepatient. These may include: a) frequency, amplitude and patterns (e.g.,bursting v. tonic) along the lateral hypothalamic and other brain tractscarrying noxious signals to the thalamus; b) changes in the mechanismsthat inhibit pain signals or neural plasticity-related changes thatresult in “amplification” of pain signals at any level of the neuraxis;and c) the emotional and cognitive modulation of pain signals at thecortical-subcortical levels. Increases in frequency, amplitude orchanges in firing pattern of neurons mediating pain disinhibition or“amplification” are likely to augment the sensation of pain. Emotions,mood or behavior shape the response to pain and the patient's reactionto it. In one embodiment of this invention, factors a), b) or c) aretaken into account to manage (prophylaxis and/or treatment) of pain.This may be accomplished through invasive or non-invasive monitoring inpatients of electrical, chemical, thermal, photonic, mechanical (e.g.,pressure, movement), cognitive/behavioral/emotional activity of nerves,roots, tracts, zones, pathways, nuclei or cortical regions, usingappropriate tools (e.g., electrodes, sensors, fMRI, PET scan,scales/questionnaires, etc.). The dependence of pain level (e.g.,tolerable, intolerable) on the factors listed above may be investigatedby determining pain thresholds to noxious stimuli in a systematic andcontrolled manner.

The difference in magnitude, rate of change or “direction” of change(increases or decreases) of the value in a pain index derived from abiological signal during an episode of pain in comparison to the sameindex when the patient is not experiencing pain at the same or differenttimes of day and under similar or different conditions (e.g.,wakefulness; attentive state, etc.), may be used to empiricallydetermine/quantify pain levels.

One or more composite pain indices may be determined from differenttypes of body signals. For example, body indices from two or moredifferent classes of signals (e.g., cardiac signals such as heart rate,heart rate variability, EKG morphology characteristics, electro-dermalor sudo-motor activity, etc.,) and kinetic signals such as thoseindicative of a patient's movement, posture, muscle activity, etc.) maybe used to derive a composite index. The composite index value during anepisode of pain may then be compared to the corresponding compositeindex value when the patient is not experiencing pain to provideinformation useful in establishing or modifying a treatment regimen.Exemplary composite indices may comprise, e.g., the sum, mean, product,difference, ratio, etc., of two or more individual indices.

Pain indices (whether individual or composite) may be adjusted orcorrected for numerous factors that may affect patient pain intensitiesand/or thresholds. Among the factors that may be used to provide suchadjustments/corrections are time of day, level of consciousness, levelof fitness, medication levels, age, sex, genetic factors, etc.

The patient pain module 380 may also comprise a pain thresholddetermination unit 460. The pain threshold determination unit 460 may beconfigured to determine a pain threshold for the patient for a certainmodality (e.g., burning). The pain threshold determination unit 460 maydetermine pain thresholds from one or more body signals, whose value(s)are suggestive of sufficient pain to merit treatment with painmedications or other pain treatments. The patient pain module 380 mayalso be used to determine a sensory threshold (i.e., the minimalstimulus intensity required to elicit a non-painful sensation) to: 1.determine if there is a change in the sensory threshold; and 2.determine if there is a change in the intensities (computed as thedifferences or ratios) of the stimulus energies required to elicit anon-painful and a painful sensation. This information may be used toassess the status of the pain disorder.

In a particular embodiment, the pain threshold determination unit 460may be configured to provide at least one stimulus to a patient, receivea response of the patient to the at least one stimulus, and determine,based on the response to the at least one stimulus, at least one painthreshold. In a particular embodiment, the pain threshold determinationunit 460 may instead by configured to determine, based on the responseto the at least one stimulus, whether at least one pain threshold haschanged.

The pain threshold determination unit 460 may, in some embodiments,determine a distress threshold and/or a suffering threshold, byextrapolating from the pain thresholds, patient workup, and/or otherdata sources the values of body signals suggestive of distress(heightened pain) and/or suffering (excruciating pain).

Pain thresholds may also be affected by emotional/behavior factors, andsuch factors may also be used to adjust pain threshold (or pain index)values. These factors may also be determined by the presentation ofstimuli with positive and/or negative emotional meaning to the patientduring threshold testing (e.g., during or proximate to the presentationof noxious stimuli as part of pain threshold testing).

Returning to FIG. 3, the communication unit 320 may be configured tocommunicate an alert if the determined pain index is below thepredetermined threshold pain index and the patient requests medication.Thus, if the pain level actually experienced by the patient at any timeis incommensurate with the pain index to which the pain level usuallycorrelates, an alert can be given to a caregiver to: a) determine if thetreatment device (e.g., sensors, modules, etc.) is operating correctly;b) if the treatment device is operating correctly, re-test painthresholds to find if they have undergone changes; c) if the thresholdremains unchanged, investigate for the development of tolerance tomedications; d) if the patient has not developed tolerance tomedications, warn the caregiver of possible drug-seeking behavior by thepatient.

Turning now to FIG. 5, a block diagram depiction of the body datacollection module 350 is provided, in accordance with one illustrativeembodiment of the disclosure. FIG. 5 depicts an exemplary implementationof the body data collection module 350 described above with respect toFIG. 3. The body data collection module 350 may include hardware (e.g.,amplifiers), tools for chemical assays, optical measuring tools, and/ora body data memory 550 for storing and/or buffering data in the bodydata collection module 350. The body data memory 550 may, in someembodiments, be adapted to store body data for logging or reportingpurposes and/or for future body data processing and/or statisticalanalyses.

The body data collection module 350 may also include one or more bodydata interfaces 510. The body data interface 510 may provide aninterface for input/output (I/O) communications between the body datacollection module 350 and body data units/modules (e.g., [560-570],[573-576]) via connection 580. The body data units/modules (e.g.,[560-570], [573-576]) may comprise various sensors for acquiring bodysignals, and may communicate with the medical device 100 via thecommunication unit 320 via connection 580. The connection 580 may be awired or wireless connection, or a combination of the two. Theconnection 580 may be a bus-like implementation or may include anindividual connection (not shown) for each, or some number, of the bodydata units (e.g., [560-570], [573-576]). The connection 580 may alsoinclude connection elements as would be known to one of skill in the arthaving the benefit of this disclosure. In various embodiments, the bodydata units may include, but are not limited to, an autonomic dataacquisition unit 560, a neurologic data acquisition unit 570, anendocrine data acquisition unit 573, a metabolic data acquisition unit574, a tissue stress marker data acquisition unit 575, a quality of life(QOL) unit (not shown in FIG. 5), and/or a physical fitness/integrityacquisition and determination unit 576.

In one embodiment, the autonomic data acquisition unit 560 may include aheart beat data acquisition unit 561 adapted to acquire aphonocardiogram (PKG), EKG, echocardiography, apexcardiography and/orthe like, a blood pressure acquisition unit 563, a respirationacquisition unit 564, a blood gases acquisition unit 565, and/or thelike. Alternatively or in addition, the autonomic data acquisition unitmay comprise an infrared imager to detect changes in the temperatureparts (e.g., face) that may be indicative of pain.

In one embodiment, the neurologic data acquisition unit 570 may containa kinetic unit 566 that may comprise an accelerometer unit 567, aninclinometer unit 568, and/or the like; the neurologic data acquisitionunit 570 may also contain a responsiveness/awareness unit 571 that maybe used to determine a patient's responsiveness to testing/stimuli(e.g., reaction time) and/or a patient's awareness of theirsurroundings. Responsiveness may be determined by asking the patient toperform simple verbal (e.g., What is your name?) or motor tasks (e.g.,raise your right hand), answer questions about orientation (e.g., Whatis today's the date; Where are you?), or more complex cognitive (e.g.,complex reaction time, memory tests), and motor tasks (e.g., close youreyes, make a first with your left hand and touch your left ear with yourright hand). When necessary, responsiveness may be assessed usingnoxious stimuli. Responsiveness may be quantified using latency to andaccuracy/correctness of responses, among others. Since certain painmedications depress the central nervous system and since decreasedresponsiveness precedes potentially serious or fatal adverse medicationeffects such as respiratory depression, bradycardia or hypotension,assessment of responsiveness is key to preventing the occurrence ofthese serious adverse effects.

Alternatively or in addition, the neurologic data acquisition unit 570may also comprise a video or infrared imager with facial recognitionsoftware or facial EMG to detect changes in facial expression indicativeof pain, and/or sound/acoustic sensors to detect sounds indicative ofpain (such as moans/groans). These lists are not exclusive, and the bodydata collection module 350 may collect additional data not listedherein, that would become apparent to one of skill in the art having thebenefit of this disclosure. The body data units [560-570], [573-576] maybe adapted to collect, acquire, receive/transmit heart beat data, EKG,PKG, echocardiogram, apexcardiogram, blood pressure, respirations, bloodgases, body acceleration data, body inclination data, EEG/ECoG, and/orthe like. The quality of life (QOL) unit (not shown in FIG. 5) may bealso used to assess the psychological status of the patient. Additionaldetails on body signal analysis are provided by other patentapplications assigned to Flint Hills Scientific, LLC or Cyberonics,Inc., such as, U.S. Ser. No. 12/896,525, filed Oct. 1, 2010; U.S. Ser.No. 13/288,886, filed Nov. 3, 2011; U.S. Ser. No. 13/449,166, filed Apr.17, 2012; and U.S. Ser. No. 13/678,339, filed Nov. 15, 2012. Each of thepatent applications identified in this paragraph is hereby incorporatedherein by reference.

The body data interface(s) 510 may include various amplifier(s) 520, oneor more A/D converters 530, and/or one or more buffers 540 or othermemory (not shown). In one embodiment, the amplifier(s) 520 may beadapted to boost and condition incoming and/or outgoing signal strengthsfor signals such as those to/from any of the body data units/modules(e.g., [560-570], [573-576])) or signals to/from other units/modules ofthe medical device 100. The A/D converter(s) 530 may be adapted toconvert analog input signals from the body data unit(s)/module(s) into adigital signal format for processing by controller 210 (and/or processor215). A converted signal may also be stored in a buffer(s) 540, a bodydata memory 550, or some other memory internal to the medical device 100or external to the medical device 100. The buffer(s) 540 may be adaptedto buffer and/or store signals received by the body data collectionmodule 350 as well as signals to be transmitted by the body datacollection module 350. In various embodiments, the buffer(s) 540 mayalso be adapted to buffer and/or store signals in the body datacollection module 350 as these signals are transmitted betweencomponents of the body data collection module 350.

As an illustrative example, in one embodiment, data related to apatient's respiration may be acquired by respiration unit 564 and sentto the medical device 100. The body data collection module 350 in themedical device 100 may receive the respiration data using body datainterface(s) 510 to determine its rate, amplitude, and/or pattern. Asthe data is received by the body data interface(s) 510, the incomingdata may be amplified/conditioned by amplifier(s) 520 and then convertedby A/D converter(s) into a digital form. The digital signal may bebuffered by a buffer(s) 540 before the data signal is transmitted toother components of the body data collection module 350 (e.g., body datamemory 550) or other components of the medical device 100. In somealternative embodiments, the body data units/modules (e.g., [560-570],[573-576])) may be housed within the medical device 100. Body data inanalog form may be also used in one or more embodiments.

Turning now to FIG. 6, a flow chart depiction of a method 600 ofperforming a patient pain analysis, in accordance with one embodiment ofthe present disclosure, is illustrated. The medical device 100 maydetect one or more patient body signals (block 610). In one embodiment,detecting at 610 may comprise transmission of one or more body signalsrecorded by the sensor 130 to the medical device 100. As describedabove, the medical device 100 may receive various autonomic data,neurological data, endocrine data, metabolic data, tissue stress markerdata, etc. Based upon the body signal(s) received, the medical device100 may determine a patient pain index (block 620). The patient painindex may be a normalized calculation of a patient pain level based uponvarious objective and/or subjective factors. The objective factors mayinclude a change in one or more indices relating to autonomic,neurological, endocrine, metabolic, and/or tissue stress markerindications in the patient's body. The subjective factors may include anindication from the patient as to the amount and/or quality (e.g.,sharp, boring, etc.) of pain being experienced by the patient. Thepatient pain index may be calculated using various mathematicalcalculations based upon various weightings attributed to one or more ofthe factors described above.

A patient pain index may then be compared to a predetermined thresholdto determine whether the pain index is at or above the threshold (block630). The predetermined threshold may be calculated and stored in themedical device 100. In one embodiment, the predetermined threshold maybe manually or automatically adjusted based upon one or more factors,such as a change in the patient's health, mood, emotional state, time ofday, sleep latency, total sleep time, number and duration of arousalsfrom sleep as well as their time of occurrence, environmental factors,patient activity factors (e.g., exercise versus sleep), the patient'sphysical fitness index, etc. In an alternative embodiment, one or morepatient pain indices may be treated as dynamic values that may beautomatically or manually adjusted/weighted (e.g. increased ordecreased) based upon the therapy history, (e.g., dose and/or type ofmedications recently delivered), an increase or decrease in the patientpain tolerance level, adverse therapy effects and safety factors, etc.In some embodiments, a customized pain threshold may be predeterminedfor a particular patient as a function of the factors listed immediatelyabove or of others. In one embodiment, one or more threshold-baseddecisions may be changed automatically by the medical device 100, or maybe changed based upon input received from an external source (e.g., thepatient or a medical professional).

Upon a determination that the patient pain index is below the painthreshold index, the medical device 100 may continue to monitor thepatient (block 640) and may continue to detect or receive one or morepatient body signals. In one embodiment, the recording, processingand/or analyses of certain patient body signals may only be triggeredbased upon programmed temporal triggers, detection of one or morechanges in body signals, other patient events, etc. For example,processing or analysis of high dimensional, computationally expensiveand weak signals such as those generated by the brain cortex, may beundertaken only when changes in the value of certain autonomic orkinetic signals reach or exceed a threshold.

Upon a determination that a patient pain index is above a predeterminedthreshold, the medical device may further determine if the patient'ssafety would be compromised by administration of a given drug, or byhigh dosage of a given drug (block 650).

Development of drug tolerance is common with certain pain medications,requiring increases in dose to attain the same effect as earlier smallerdoses. This phenomenon may be detected and quantified by comparing theeffects on various autonomic, neurologic and other indices as a functionof time. By way of a non-limiting example, changes in pupillary size(e.g., myosis) are caused by opioid analgesics such as morphine.Measurements of pupillary size before and after administration of acompound (when Cmax is reached or at some pre-specified time), arerecorded over time for identical doses; if the change (“delta”) inpupillary size decrease with the number of administered doses and/or thelatency to maximal myosis lengthens, tolerance has occurred and itsdegree and rate may be then determined. Side effects may be alsodetected and quantifies (latency to onset, magnitude and duration) usingneurologic (e.g., reaction time, attention, posture, coordination, etc.)or autonomic (heart rate, respiratory rate, blood pressure, etc.) amongother body signals. Using information from representative patients'samples, changes in normative values in autonomic, neurologic or othersystems for a given analgesic compound, dose, route of administrationamong others are compared to those observed in an individual.

In one embodiment, a body tolerance index associated with the patient isdetermined. The body tolerance index may be calculated based uponvarious factors, such as patient weight, height, age, health status,medications provided to patient previously, etc. The body toleranceindex may be compared to a baseline reference tolerance index range forthe patient chosen from the naïve (e.g., the patient has not beenexposed to a medication or to similar medications, or after having beentreated). The body tolerance index may refer to the rate and degree towhich the patient's response to a medication is lessened or blunted byrepeated exposures.

Using changes, if any, in the values of a patient's biological data as afunction of repeated exposures to pain medications, a Drug ToleranceIndex (DTI) may be calculated as follows:DTI=ΣδMn(bi)/E+ΣδLn(bi)/Ewhere δM is the magnitude of a change, δL is latency change, bi is abody index, n(bi) is the number of body indices used in the calculationand E is the number of exposures. E is placed in the denominator sincethe tolerance decreases with the number of exposures (e.g., it tendstowards a “plateau”). DTI may be also calculated using the change indose required to obtain the same effect (as when the patient receivedthe first or some other dose) with repeated exposures to a medication.The actual doses of medications may be also used. DTI may be a negativeor positive integer depending on whether the change or “delta” is deemedpositive or negative.

Upon a determination that the patient has developed tolerance to amedication or therapy (this phenomenon may also occur with electrical,thermal or other forms of therapy), the medical device 100 may select ordetermine the type of medication and the dosage of the selectedmedication (block 660) or another type of therapy and parameters thereoffor delivery to the patient. For example, if the tolerance formedication seems particularly high, the dosage of a particularmedication may be increased. An increase or decrease in dosage may bepermanent or temporary. Based upon the type and the dosagedetermination, the medical device 100 may deliver the medication byactivating the medication dispenser 340 (block 680).

A Drug Adverse Index (DAI) may be calculated using an approach similarto that described above for DTI using body signals. For example theeffect of administering a certain narcotic at a certain dose on heartand respiratory rate, blood pressure, reaction time, etc. and thelatency to for example the maximal change in said body signals, may bequantified and used to compute a DAI. In one embodiment of thisdisclosure, if any change in the values of the DAI is, for example, atleast one standard deviation from the mean, an adverse event may bedeclared, a warning issued and the relevant information logged intomemory.

A scale, such as from 0-1 (0 for no subjective effect and 1 for the mostsevere one) may be applied to quantify adverse effects. This disclosuretakes into account that not all adverse effects give rise to symptomsand that monitoring of body indices is necessary to detect them.Hypertension caused by a drug is highly unlikely to be associated withany symptoms and drugs that depress consciousness reduce the patient'sability to feel and/or report symptoms.

In some embodiments, a discomfort level for the patient may bedetermined. Discomfort herein refers to another manifestation of pain.The discomfort level is defined herein as either (or both) of a lack ofstillness or quietness that may be “quantified” by the patient using anumerical or a pictorial scale or objectively, as an index based on therecording and analyses of body signals. Patients that are uncomfortableare fidgety or restless and also have facial expressions and uttersounds (formed or non-formed vocalizations) correlated with the level ofdiscomfort. As a non-limiting example, facial EMG or facial imaging, therecording of formed or non-formed vocalizations or of other sounds(e.g., turning in bed), the recording of the number/unit time (rate),amplitude, velocity, direction of body movements, may be used to computea discomfort level (the higher its value, the higher the discomfortlevel). Behavioral evidence of discomfort may manifest before or after apatient complains of pain. A discomfort threshold may be set for eachpatient at or above which an intervention (e.g., a medication,repositioning of the patient's body, psychological support, etc.) isperformed. The discomfort threshold may be based upon various body dataand may express the magnitude and/or rate of increase in pain or anabsence of pain above a certain level if the index is 0.

Turning now to FIG. 7A, a flowchart depiction of a method 700, anexemplary operation of the medical device 100 following an input fromthe patient requesting medication, in accordance with one embodiment ofthe present disclosure, is provided. The patient may send a request formedication to the medical device 100. The medical device 100 may receivethe input from the patient regarding the request for medication (block710). Upon receiving such an input, the medical device 100 may determinewhether a minimum time period has elapsed since the delivery of the lastdosage (block 720). The minimum time period may be based uponpredetermined ranges selected and programmed by a medical professionalor may be based on one or more of a safety index, a tolerance index or apain level. In an alternative embodiment, the predetermined ranges maybe adjusted dynamically (e.g., weighted linearly or non-linearly) basedon various factors, such as various patient body data levels, painthreshold levels, dosage levels previously administered, discomfortlevel, time of day, patient's mood, etc.

Upon a determination that the minimum time period has not elapsed sincethe last dosage, an indication by the medical device 100 may provide anindication of unavailability for medication delivery (block 730). Uponan indication of unavailability of medication, the medical device 100may notify one or more entities, such as a medical professional, and/orrecord the event (block 740) or perform a more detailed and extensiveanalyses of relevant to determine if based on need and safety a therapymay be provided even though the pre-specified time criterion has notbeen met Upon a determination that minimum time period has indeedelapsed since the last dosage, in response to the input from thepatient, the medical device 100 may perform an independent analysis todetermine whether or not to automatically deliver pain medication. Thisanalysis may be based upon the detection of body data and the comparisonof the pain index to the threshold described in FIG. 6. Therefore,despite the fact that a patient has requested medication, an independentevaluation of the patient's pain being at or above a particularthreshold may be made before delivering the patient's medication.Further, automated delivery of pain medication may be performed withoutinput from the patient. In this manner, before the onset of pain,various body data may indicate that pain is impending, and automateddelivery of medication may be provided to the patient. In this manner,the onset of pain (or worsening of pain) even may be prevented by theautomated delivery of pain medication or of another therapy.

In another embodiment, a decision to automatically withhold or delivermedication may be based, not on time elapsed from the last drug deliveryand/or the amount of medication given to a patient, but on body valueindices. If a time constraint has been set (e.g., medication is to bedelivered every 4 hours) and a patient request medication 2 hours afterthe last dose, the device may perform analyses of body indices and basedon the results assess the safety of drug administration at that time; ifdeemed safe, the time constraint may be ignored. Adjustments in the dosedelivered (lower or higher than programmed) may be automaticallyperformed by the device based on quantification and analyses of bodyindices correlated with pain level and those indicative of safety ofadministration.

Turning now to FIG. 7B, a flowchart depiction of a method 701, anexemplary operation of the medical device 100 following an input fromthe patient requesting medication, in accordance with one embodiment ofthe present disclosure, is provided. Elements 710-740 are generallysimilar to the like-numbered steps of FIG. 7A and need not bere-discussed.

Upon a determination at 720 that the minimum time period has elapsedsince the last dosage, a determination may be made at 750 as to whetherdrug delivery at the present time would be safe.

The determination at 750 may comprise any of those discussed infra(e.g., responsiveness tests). For example, the responsiveness test maycomprise a determination as to whether the patient's responsiveness isabove a responsiveness threshold, such as a responsiveness thresholdcorresponding to the patient having normal responsiveness. Moregenerally, a responsiveness threshold may be set such that a finding bythe test that the patient's responsiveness is below it, reflects atleast one of a slowing of the patient's reaction time, an increase ofthe number of incorrect responses given by the patient, an increase inthe number and/or magnitude of results indicative of impaired cognition,a state of lethargy from which the patient is easily arousable and willremain awake without further stimulation, a state of patient lethargyfrom which the patient is arousable but will only remain awake withfurther stimulation, or a state of patient stupor from which the patientis difficult to arouse or a coma from which the patient is unarousable.

If the minimum time period has not elapsed, flow may move to blocks 730and 740. If the minimum time period has elapsed, then drug delivery maybe performed (block 760). Therefore, despite the fact that a patient hasrequested medication, an independent evaluation of the whether drugdelivery would be safe may be made before delivering the patient'smedication.

Turning to FIG. 8, a flowchart depiction of a method 800 in accordancewith one embodiment of the present disclosure is provided. Generally,the method 800 assumes a patient is undergoing a treatment for pain asdescribed herein, and as part of that treatment, a pain threshold of thepatient has been previously determined. In the method 800, the patient'spain threshold may be tested at 810 using any appropriate apparatusand/or technique, such as those described elsewhere herein. Generally,noxious stimuli of increasing intensity may be applied to the patientuntil he or she reports perception of pain. Further, distress and/orsuffering thresholds, if desired, may be determined by extrapolationand/or other operations.

A determination may then be made at 820 as to whether the patient's painthreshold has changed, based on the results of the test at 810 and theprevious determination of the patient's pain threshold. If the patient'spain threshold has not changed, i.e., is stable, the present treatmentplan may be continued at 830 and delivered at 850. If the patient's painthreshold has changed, the present treatment plan may be modified at840. Modification at block 840 may comprise one or more of changingtherapy parameters (increasing a dose or frequency of therapy delivery),switching therapy modality (e.g., from drug delivery to electricalstimulation), or adding a therapy modality (e.g., adding electricalstimulation to ongoing drug delivery). The therapy modified at 840 maythen be delivered at 850.

Turning to FIG. 9, a flowchart depiction of a method 900 in accordancewith one embodiment of the present disclosure is provided. The patientmay send a request for medication to the medical device 100 (block 910).Upon receiving such an input, the medical device 100 may determinewhether the patient's pain index has increased (block 920). If it has,it may be concluded that the patient's request indicates an increase inhis or her pain burden, and the requested treatment may be delivered tothe patient (block 930). If it has not, it cannot be determined whetherthe patient's request is not appropriate in light of his or her pain(i.e., drug-seeking behavior?) or whether the patient's pain thresholdhas decreased, such that the same pain index value is now relativelyhigher than formerly. Thus, the patient's pain threshold may be tested(block 940), comparably to that performed at FIG. 8, block 810.

Thereafter, if it is determined at 950 that the patient's pain thresholdhas decreased, treatment may be delivered at 930. If the patient's painthreshold has not decreased, then the patient may be exhibitingdrug-seeking behavior, and the delivery of treatment may be refused at960.

FIG. 10 relates to a method 1000 involving patient pain threshold testsin the context of changes in the patient's emotional and/or mentalstatus, in accordance with one embodiment of the present invention.Specifically, if it is determined at 1010 that the patient's emotionaland/or mental status has changed, then the patient's pain threshold maybe tested (block 1020), comparably to that performed at FIG. 8, block810. If the patient pain threshold is determined at 1040 to havechanged, then the patient's treatment plan may be changed at 1050. Onthe other hand, if it were determined at 1010 that no emotional and/ormental status change occurred, then the patient's treatment plan may becontinued at 1020. Whether continued at 1020 or changed at 1050,treatment may be delivered at 1060.

FIG. 11 provides a flowchart depiction of a method 1100, relating tomeasures of responsiveness and/or awareness as indicators of safety ofadministration of CNS depressant drugs and guides for the delivery oftreatment for pain. The patient's responsiveness and/or awareness may betested (block 1110), such as at a time when the medical device 100 ispreparing to deliver a pain therapy. More information regardingresponsiveness and/or awareness testing may be found in U.S. patentapplication Ser. No. 12/756,065, filed Mar. 7, 2010, hereby incorporatedherein by reference.

If either or both of responsiveness or awareness have not decreasedrelative to a reference value (the reference may be obtained from anaïve patient (has not received drugs) or at different times afteradministration of a medication) the current treatment plan may becontinued with delivery at 1130. If either or both are determined at1120 to have decreased, safety of administration of a CNS depressantdrug or therapy (e.g., cooling of a brain region) is re-assessed. Thus,one or more body signals from the patient may be recorded and/oranalyzed at 1140. Exemplary body signals include heart rate, respiratoryrate, blood pressure, etc. If one or more body signals are determined at1150 to be depressed below a certain value, i.e., are indicative ofimpaired function of the patient's body activity, then his or hertreatment plan may be modified (block 1170). If not, his or hertreatment plan may be continued at 1160. Whether continued at 1160 ormodified at 1170, treatment may then be delivered at 1180. Whileemphasis on the use of awareness and responsiveness testing has beenplaced on safety of drug administration, these two signals may be usedto estimate pain level and its impact on a patient's ability to functionat a certain cognitive level. For example, attention span is susceptibleto degradation by pain.

FIG. 12 provides a flowchart depiction of a method 1200 in accordancewith one embodiment of the present disclosure. A body signal from apatient may be recorded, processed, and/or analyzed at 1210. In someembodiments, this may be done automatically by a device, in response toreceiving at the device a request for delivery of a pain therapy to thepatient or in response to a change in a body signal. From the bodysignal, a pain level may be determined at 1220. The pain level may havechanged, as determined at block 1230. If it has lowered (determined atblock 1240), it may then be determined at block 1250 whether it is safeto deliver a drug treatment for pain. In some embodiments, the safetydetermination at 1250 may comprise determining the patient's vitalsigns, coordination, consciousness, and/or awareness at 1255.

If the safety determination at 1250 reports drug delivery would beunsafe, a non-drug treatment (e.g., an electrical stimulation, etc.) maybe delivered at 1260. If the safety determination at 1250 reports drugdelivery would be safe, a drug may be delivered at 1270.

After delivery of the drug (block 1270), it may be determined whetherdrug delivery was efficacious (block 1280), i.e., whether it relievedthe patient's pain. If it did, flow may return to block 1210 to beginanother iteration of the method 1200. However, if drug delivery was notefficacious, or if it is not safe or convenient to deliver moremedications, a non-drug treatment may be delivered at 1260.

After a non-drug treatment may be delivered at 1260, flow may return toblock 1210 to begin another iteration of the method 1200.

In some embodiments, the present disclosure may provide a method forproviding pain medication, comprising: receiving, at a device, a requestfor delivery of a pain medication to a patient; receiving, automaticallyby the device, at least one body data value or a series of values ofsaid patient's body signal(s) in response to the request for delivery ofa pain medication; determining a patient pain index based upon the bodydata series; determining whether the patient pain index is above areference pain index or pain level; determining a safety index; andallowing, automatically, delivery of a pain medication based on at leastone of the safety index or a determination that the patient pain indexis above the reference pain index.

In some embodiments of this disclosure, delivery of a therapy may beautomatically prompted in response to the value of at least one bodyindex or a change in said value. This prompt may or may not be carriedout depending on the safety index.

In some embodiments of this method, allowing delivery of the medicationmay comprise determining a first dosage of medication received by thepatient during a first previous time period; determining whether asecond time period has elapsed since the patient received the firstdosage, wherein the second time period is based upon the type ofmedication and first dosage; determining a second dosage of medication(and the type of medication) to deliver to the patient based uponwhether or not the second time period has elapsed since the patientreceived the first dosage and the type of medication the patient hadreceived; and delivering the second dosage of medication to the patientin response to the second time period having elapsed or the type ofmedication the patient received. Alternatively or in addition, at leastone of determining a patient pain index and determining a safety indexcomprises recording and analyzing at least one body signal to compute apain index and administering at least one of a patient responsivenesstest and/or a patient awareness test and wherein allowing delivery of apain medication is based on a determination that the patient pain indexis above the reference pain index and a determination that the patient'sresponsiveness exceeds a responsiveness safety threshold. In someembodiments, the safety index may be based on neurological signals otherthan responsiveness and/or awareness or on autonomic, metabolic,endocrine, or tissue-stress marker signals.

This method may further comprise automatically implementing or changinga delivery of a pain medication if at least one of a pain level is abovea certain reference value, a pain threshold is below a certain referencevalue, a body tolerance is above a certain reference value, an emotionalstate is negative, or the pain index is above a reference value.

In another embodiment, the present disclosure provides a method forproviding pain medication to a patient, comprising receivingautomatically, at least a first body data value or series of values of apatient; determining a first discomfort index of the patient based uponthe first body data value or series; determining whether the firstdiscomfort index exceeds a first discomfort index threshold; andproviding a first therapy in response to determining that the firstdiscomfort index exceeds the first comfort index threshold.

This method for providing pain medication may further comprise receivinga second body data value or series of values of the patient; determininga second discomfort index of the patient based upon the second body datavalue or series of values; determining whether the second discomfortindex exceeds a second discomfort index threshold; determining a secondtherapy in response to determining that the second discomfort index doesexceed the second discomfort index threshold; and providing the secondtherapy to the patient.

In another embodiment, the present disclosure provides a method,comprising receiving at a device, a request for delivery of a paintherapy to a patient; receiving, automatically by the device, at leastone body data value or series of values in response to the request fordelivery of a pain therapy; determining a patient pain index based uponthe body data value or series or values; determining whether the patientpain index is above a patient pain index threshold; and automaticallydelivering a pain therapy to the patient in response to determining thatthe patient pain index is above the patient pain index threshold. Thismethod may further comprise administering a responsiveness test to thepatient, wherein automatically delivering a pain therapy comprisesdelivering a pain therapy in response to determining that the patientpain index is above the patient pain index threshold and determiningthat the patient's responsiveness exceeds a responsiveness threshold.

In another embodiment, the present disclosure provides a method forproviding pain medication, comprising receiving at least one of arequest for delivery of a pain medication from a patient, an indicationof an elapsed time period, or a request for administration of aresponsiveness test to a patient; administering a responsiveness test tothe patient in response to the receiving; and allowing delivery of apain medication based on a determination that the patient'sresponsiveness is above a certain responsiveness threshold. In thismethod, the determination that the patient's responsiveness is above theresponsiveness threshold may correspond to the patient having normalresponsiveness.

Alternatively or in addition, this method may further comprise receivingat least one body data value or series of values of the patient inresponse to a determination that the patient's responsiveness is notabove the responsiveness threshold; determining at least one of heartrate, respiration rate, blood pressure, and oxygen saturation based onthe at least one body data value or series of values; determiningwhether the at least one heart rate, respiration rate, blood pressure oroxygen saturation is below a reference heart rate threshold, respirationrate threshold, blood pressure threshold, or oxygen saturationthreshold; and allowing delivery of a pain medication based on adetermination that the at least one of a heart rate, respiration rate,blood pressure or oxygen saturation is above said reference heart ratethreshold, respiration rate threshold, blood pressure threshold, oroxygen saturation threshold. This method may further comprise performingan action selected from suspending a treatment plan and modifying atreatment plan based on a determination that the at least one of a heartrate, respiration rate, blood pressure or oxygen saturation is below areference heart rate threshold, respiration rate threshold, bloodpressure threshold, or oxygen saturation threshold.

The particular embodiments disclosed above are illustrative only as thedisclosure may be modified and practiced in different but equivalentmanners apparent to those skilled in the art having the benefit of theteachings herein. Furthermore, no limitations are intended to thedetails of construction or design herein shown other than as describedin the claims below. It is, therefore, evident that the particularembodiments disclosed above may be altered or modified and all suchvariations are considered within the scope and spirit of the disclosure.Accordingly, the protection sought herein is as set forth in the claimsbelow.

In some embodiments, the present disclosure may relate to one or more ofthe following numbered paragraphs.

101. A method for pain prophylaxis or prevention comprising at least oneof:

determining a pain threshold and comparing said threshold to a painthreshold reference value;

determining a body tolerance index and comparing said body toleranceindex to a body tolerance index reference value;

determining a pain index and comparing said pain index to a pain indexreference value;

determining a safety index and comparing said safety index to a safetyindex reference value;

determining an emotional state of the patient and comparing it to apositive emotional state reference value; and

automatically delivering a pain treatment regimen if at least one of:

the pain threshold is below the pain threshold reference value;

the body tolerance index is above the body tolerance index referencevalue;

the pain index is above the pain index reference value;

the safety index is above the safety index reference value; and

the emotional state is below said positive emotional state referencevalue.

201. A medical device system for providing medication to a patient, themedical device comprising:

a first receiver for receiving at least one body signal from a patient;

a controller operatively coupled to said receiver, said controlleradapted to:

determine a patient pain index based at least in part on said at leastone body signal;

compare said patient pain index to a first reference value; and

determine at least one treatment parameter based upon comparing saidpain index to a reference value; and

a therapy unit to cause an application of a medication in response tosaid comparing of said pain index being outside said reference value.

202. The medical device system of numbered paragraph 201, wherein saidbody signal comprises at least one of heart beat data, blood pressuredata, respiration data, blood gas data, neurological data, endocrinedata, metabolic data, or tissue stress marker data.

203. The medical device system of numbered paragraph 201, wherein saidmedical device further comprises:

a reservoir to store at least one medication;

a medication dispenser operatively coupled to said reservoir, saidmedication dispenser adapted to extract medication from said reservoir;

a body data collection module adapted for receiving said at least onebody signal;

a patient pain module to determine a patient pain index based leastpartially upon said body signal; and

a controller adapted to control at least one operation of saidmedication dispenser based upon said patient pain module.

204. The medical device system of numbered paragraph 203, wherein saidmedication dispenser is a pumping device that is capable of pumpingmedication from the reservoir to the patient.

205. The medical device system of numbered paragraph 205, wherein atleast one of a different medication or a different pain treatmentregimen are delivered to the patient if the safety index is below thesafety index reference value and one of:

the pain threshold has decreased since the administration of a firstpain treatment regimen;

body tolerance has developed since the administration of a first paintreatment regimen;

the pain index is above the pain index reference value;

the patient's emotional state is negative.

206. The medical device system of numbered paragraph 205, wherein anon-pharmacological treatment is delivered if at least one of the painthreshold is below the pain threshold reference value, the bodytolerance index is above the body tolerance index reference value, thepain index is above the pain index reference value, the patient'semotional state is negative, or the safety index is indicative of highrisk of adverse events.

301. A non-transitory computer readable program storage unit encodedwith instructions that, when executed by a computer, perform a method,comprising:

receiving, automatically at the device, at least one body data series;

determining a patient pain index based upon said body data series;

determining whether the patient pain index is above a patient pain indexreference value;

automatically delivering a pain therapy to the patient in response todetermining that said patient pain index is above said patient painindex reference value.

401. A medical device system for providing medication to a patient, themedical device comprising:

a first receiver for receiving at least one body signal from a patient;

a controller operatively coupled to said receiver, said controlleradapted to:

determine a patient pain index based at least in part on said at leastone body signal;

determine if said patient pain index is commensurate with the patient'ssubjective pain level

determine at least one treatment parameter based upon comparing saidpain index being commensurate with said patient's subjective pain level;and

a therapy unit to cause an application of a medication in response tosaid determination that the pain index is commensurate with thepatient's subjective pain level.

501. A medical device system for providing medication to a patient, themedical device comprising:

a first receiver for receiving at least one body signal from a patient;

a controller operatively coupled to said receiver, said controlleradapted to:

determine a patient pain index based at least in part on said at leastone body signal;

determine if said patient pain index is commensurate with the patient'ssubjective pain level

a therapy unit to withhold an application of a medication in response tosaid determination that the pain index is not commensurate with thepatient's subjective pain level.

What is claimed is:
 1. A medical device system, comprising: at least onesensor configured to sense at least one body signal from a patient; anda medical device configured to: receive at least a first sensed bodysignal from the at least one sensor; determine a patient pain index,wherein the patient pain index is based at least in part on the firstsensed body signal; determine whether the patient pain index is above atleast a first pain index threshold, wherein the first pain indexthreshold is indicative of a level of pain below a pain perceptionthreshold; select a pain treatment regimen based on a determination thatthe patient pain index is above the first pain index threshold; anddeliver the pain treatment regimen.
 2. The medical device system ofclaim 1, further comprising determining whether the patient pain indexis above a second pain index threshold, wherein the second pain indexthreshold is indicative of a pain perception threshold and the firstpain index threshold is indicative of a level of pain below the painperception threshold.
 3. The medical device system of claim 2, furthercomprising determining whether the patient pain index is above a thirdpain index threshold, wherein the third pain index threshold isindicative of the patient being in a state of distress or suffering. 4.The medical device system of claim 1, wherein the first pain indexthreshold is selected such that the pain treatment regimen is deliveredbefore the patient perceives pain.
 5. The medical device system of claim1, wherein the delivery of the pain treatment regimen occurs before thepatient perceives pain.
 6. The medical device system of claim 1, whereinthe medical device is implanted in the body of the patient and the paintreatment regimen comprises at least one of a medication, a dose of themedication, a delivery route of the medication, a cocktail ofmedications, a dose of the cocktail, a delivery route of the cocktail,an electrical stimulation, at least one parameter of the electricalstimulation, a target tissue of the electrical stimulation, a cognitivetherapy, at least one parameter of the cognitive therapy, a biofeedback,at least one parameter of the biofeedback, a thermal manipulation, atleast one parameter of the thermal manipulation, or a target tissue ofthe thermal manipulation.
 7. The medical device system of claim 1,wherein the first sensed body signal is a formed or non-formedvocalization of the patient.
 8. The medical device system of claim 1,wherein selecting a pain treatment regimen comprises one of: modifyingat least one parameter of a previously applied pain treatment regimen,or modifying a previously applied treatment modality to a differenttreatment modality; and wherein delivering the pain treatment regimencomprises applying the modified pain treatment regimen to the patient.9. The medical device system of claim 1, wherein the medical device isfurther configured to determine a body tolerance index relating to afirst medication for the patient based at least in part on, a subjectiveresponse of the patient to a first exogenous painful stimulus, or aresponse of the patient pain index to a second exogenous painfulstimulus.
 10. The medical device system of claim 1, further comprising:a pain threshold determination unit configured to provide at least onestimulus to a patient, receive a response of the patient to the at leastone stimulus, determine, based on the response to the at least onestimulus, whether at least one pain threshold has changed, and notifythe medical device to modify at least one parameter of a previouslyapplied pain treatment regimen when the at least one pain threshold haschanged.
 11. The medical device system of claim 1, wherein the medicaldevice comprises: an electrical current generator; an electrode coupledto the electrical current generator and operable to apply electricalstimulation to a nerve, organ, or structure of the patient's body; abody data collection module adapted for receiving a first body dataseries of the patient from the at least one sensor; a patient painmodule configured to determine at least one of a patient pain index or apain level; a controller adapted to control at least one operation ofthe electrical current generator based upon at least one output of thepatient pain module; a memory for storing data; and a communication unitto provide communications between the medical device and at least onedevice external to the medical device.
 12. The medical device system ofclaim 11, further comprising: a body tolerance module configured toprovide a body tolerance index based at least upon a tolerance of thepatient to the electrical stimulation.
 13. The medical device system ofclaim 11, wherein the patient pain module comprises: a pain indexdetermination unit for determination of a patient pain index based uponthe body data; a patient input unit for receiving an input relating toat least one of a patient input of a pain level experienced by thepatient and a request for electrical stimulation; and a pain indexcomparison unit for comparing the determined pain index to the firstpain index threshold.
 14. The medical device system of claim 11, whereinthe body data comprises at least one of electrical, thermal, mechanicalor chemical activity recorded from a peripheral nerve, a nerve plexus, adorsal root, a dorsal root ganglion, a spinal cord, or a brain of thepatient.
 15. The medical device system of claim 11, further comprisingan external device adapted to communicate with the communication unitand at least one of: an autonomic data acquisition unit for receivingautonomic data; a neurological data acquisition unit for receivingneurological data; an endocrine data acquisition unit for receivingendocrine data; a metabolic data acquisition unit for receivingmetabolic data; and a tissue stress marker data acquisition forreceiving tissue stress marker data.
 16. A method for providingelectrical stimulation, comprising: receiving, at a device implantedinside the body of a patient, a request for delivery of an electricalstimulation to the patient; receiving, automatically by the device, atleast one body data series of the patient in response to the request fordelivery of the electrical stimulation; determining a patient pain indexbased upon the body data series; determining whether the patient painindex is above a reference pain index; and allowing, automatically,delivery of an electrical stimulation based on a determination that thepatient pain index is above the reference pain index.
 17. The method ofclaim 16, wherein allowing delivery of an electrical stimulationcomprises: determining at least one of an intensity, frequency,polarity, pulse width, duration, or waveform of a first dosage of anelectrical stimulation received by the patient during a first previoustime period; determining whether a second time period has elapsed sincethe patient received the first dosage, wherein the second time period isbased upon the first dosage; determining at least one of an intensity,frequency, polarity, pulse width, duration, or waveform of a seconddosage of an electrical stimulation to deliver to the patient based uponwhether or not the second time period has elapsed since the patientreceived the first dosage; and delivering the second dosage of anelectrical stimulation to the patient in response to the second timeperiod having elapsed.
 18. The method of claim 17, further comprisingautomatically changing at least one of a time of delivery, intensity,frequency, polarity, duration, or waveform of an electrical stimulationif at least one of a pain threshold is above a reference value, a bodytolerance is above a reference value, an emotional state is negative, orthe pain threshold is below a reference value.
 19. The method of claim16, wherein determining a patient pain index comprises administering atleast one of a patient responsiveness test and a patient awareness test.20. The method of claim 19, further comprising: determining a safetyindex by at least administering a patient responsiveness test, whereinthe responsiveness test includes a reaction time test; and wherein theallowing delivery of an electrical stimulation comprises allowingdelivery of an electrical stimulation in response to a determinationthat the patient's responsiveness is not below a responsivenessreference value.
 21. A medical device system, comprising: an electricalcurrent generator implanted in the body of a patient; an electrodecoupled to the electrical current generator and operable to applyelectrical stimulation to a nerve, organ, or structure inside thepatient's body; a body data collection module adapted for receiving afirst body data series of the patient from at least one sensor; apatient pain module configured to determine a patient pain index basedat least in part on the first body data, wherein the patient pain moduleis further configured to determine whether the patient pain index isabove at least a first pain index threshold; and a controller adapted tocontrol the electrical stimulation from the electrical current generatorbased upon at least a determination of the patient pain module that thepatient pain index is above the first pain index threshold.
 22. Themedical device system of claim 21, wherein the first body data comprisesa formed or non-formed vocalization of the patient.
 23. The medicaldevice system of claim 21, wherein the patient pain module is configuredto determine whether the patient pain index is above the first painindex threshold and below a pain perception threshold; and wherein thecontroller controls the electrical stimulation from the electricalcurrent generator based upon at least a determination of the patientpain module that the patient pain index is above the first pain indexthreshold and below the pain perception threshold.
 24. The medicaldevice system of claim 23, wherein the first pain index threshold isselected such that the electrical stimulation is applied before thepatient perceives pain.
 25. The medical device system of claim 24,further comprising: a body tolerance module configured to provide a bodytolerance index based at least upon a tolerance of the patient to theelectrical stimulation.
 26. The medical device system of claim 23,wherein the patient pain module further comprises: a pain indexdetermination unit for the determination of a patient pain index basedupon the body data; a patient input unit for receiving an input relatingto at least one of a patient input of a pain level experienced by thepatient and a request for electrical stimulation; and a pain indexcomparison unit for comparing the determined pain index to the firstpain index threshold.
 27. The medical device system of claim 23, whereinthe body data comprises at least one of electrical, thermal, mechanicalor chemical activity recorded from a peripheral nerve, a nerve plexus, adorsal root, a dorsal root ganglion, a spinal cord, or a brain of thepatient.
 28. The medical device system of claim 27, further comprising:an emotional state unit configured to determine an emotional state,wherein the emotional state unit is configured to provide at least oneof an emotional stimulus or a psychological stimulus to the patient,receive a response from the patient to the at least one of an emotionalstimulus or a psychological stimulus; and determine, based on theresponse to the at least one of an emotional stimulus or a psychologicalstimulus, whether at least one pain threshold has changed.
 29. Themedical device system of claim 23, further comprising: a pain thresholddetermination unit configured to provide at least one stimulus to apatient, receive a response of the patient to the at least one stimulus,determine, based on the response to the at least one stimulus, whetherat least one pain threshold has changed, and notify the medical deviceto modify at least one parameter of a previously applied electricalstimulation when the at least one pain threshold has changed.
 30. Amedical device system, comprising: at least one sensor configured tosense at least one body signal from a patient; and a medical deviceconfigured to: receive at least a first sensed body signal from the atleast one sensor; determine a patient pain index, wherein the patientpain index is based at least in part on the first sensed body signal;determine whether the patient pain index is above at least a first painindex threshold; select a pain treatment regimen based on adetermination that the patient pain index is above the first pain indexthreshold; and deliver the pain treatment regimen, wherein the deliveryof the pain treatment regimen occurs before the patient perceives pain.31. The medical device system of claim 30, wherein the first body signalcomprises at least one of a pupil's size or a pupil's size variability.32. The medical device system of claim 30, wherein the first body signalcomprises at least one of a: heart rate, heart rate variability, bloodpressure, blood pressure variability, skin resistance, skin resistancevariability, respiratory rate, respiratory rate variability, oxygensaturation, or oxygen saturation variability.
 33. The medical devicesystem of claim 30, wherein the first body signal comprises at least oneof a: gastric motility, gastric motility variability, motor activity,motor activity variability, rate and loudness of formed and non-formedvocalizations, or variability of rate and loudness of formed andnon-formed vocalizations.
 34. A medical device system, comprising: atleast one sensor configured to sense at least one body signal from apatient; and a medical device configured to: receive at least a firstsensed body signal from the at least one sensor; determine a patientpain index, wherein the patient pain index is based at least in part onthe first sensed body signal; determine based at least on a change ofpupillary size whether the patient pain index is above at least a firstpain index threshold; select a pain treatment regimen based on adetermination that the patient pain index is above the first pain indexthreshold; and deliver the pain treatment regimen.
 35. The medicaldevice system of claim 34, wherein the at least one body signalcomprises at least one of a: pupillary size; speed of change ofpupillary size; frequency of changes in pupillary size per unit time;pupillary shape; or speed, magnitude and frequency of pupillary sizechanges in response to light, darkness, noxious stimuli, emotionalstimuli, cognitive stimuli, or administration of a treatment regimen.36. The medical device system of claim 34, wherein determining a patientpain index comprises administering at least one of a patientresponsiveness test and a patient awareness test.
 37. The medical devicesystem of claim 34, further comprising determining whether the patientpain index is above a second pain index threshold, wherein the secondpain index threshold is indicative of the patient being in a state ofdistress or suffering.
 38. The medical device system of claim 34,wherein selecting a pain treatment regimen comprises one of: modifyingat least one parameter of a previously applied pain treatment regimen,or modifying a previously applied treatment modality to a differenttreatment modality; and wherein delivering the pain treatment regimencomprises applying the modified pain treatment regimen to the patient.39. A medical device system, comprising: at least one sensor configuredto sense at least one body signal from a patient; and a medical deviceconfigured to: receive at least a first sensed body signal from the atleast one sensor; determine a patient pain index, wherein the patientpain index is based at least in part on the first sensed body signal;determine whether the patient pain index is above at least a first painindex threshold; determine whether the patient pain index is above asecond pain index threshold, wherein the second pain index threshold isindicative of a pain perception threshold and the first pain indexthreshold is indicative of a level of pain below the pain perceptionthreshold; select a pain treatment regimen based on a determination thatthe patient pain index is above the first pain index threshold; anddeliver the pain treatment regimen.
 40. The medical device system ofclaim 39, wherein the body data comprises at least one of electrical,thermal, mechanical or chemical activity recorded from a peripheralnerve, a nerve plexus, a dorsal root, a dorsal root ganglion, a spinalcord, or a brain of the patient.
 41. The medical device system of claim39, wherein the at least one body signal comprises at least one of a:pupillary size; speed of change of pupillary size; frequency of changesin pupillary size per unit time; pupillary shape; or speed, magnitudeand frequency of pupillary size changes in response to light, darkness,noxious stimuli, emotional stimuli, cognitive stimuli, or administrationof a treatment regimen.
 42. The medical device system of claim 39,wherein the determination that the patient pain index is above the firstpain perception threshold is based on a change of pupillary size. 43.The medical device system of claim 39, wherein the medical device isfurther configured to determine a body tolerance index relating to afirst medication for the patient based at least in part on, a subjectiveresponse of the patient to a first exogenous painful stimulus, or aresponse of the patient pain index to a second exogenous painfulstimulus.